text:
Rob And she uses the word signifies, which means giving the meaning of something. The sari obviously has an emotional attachment for her. Dick in ass porn Zona gay
Clothes moths often damage improperly stored articles. When storing susceptible items, be sure they are clean and pest free, and place them in an airtight container. You can place insect repellents such as herbal oils into the storage container, but little is known about their effectiveness. Twilight star gay sex with jonas popular sex games
Just another teen movie I bought this hoodie mainly for working out and running which is why I like the fact that s its a little loose, giving me that freedom in mobility. Even though I use it to workout, I also wear it just as an everyday hoodie and it also looks great. Love the colors! ... read more Terry nova hardcore
Also, when driving, white people love putting their turn signal on about a half mile before the turn. Just fuck my ass
Pretty blonde girl pictures This didn t sit well with the Williamses. John, who works for the Montana Department of Corrections, often interacts with people facing the reality of our finite time on Earth. If you re spending the rest of your life in prison, you know, it makes you think about the mortality of life, he says. What s important is not how long you live, but rather what you do with the life you re given. MaryMargret feels the same way. For years she has worked in a local dermatology office. She knows all too well the cultural pressures to stay young, and wishes more people would embrace the inevitability of getting older. You get wrinkles, you get old, that s part of the process, she says. Freeadult porn Sex insult
Exactly. As an American living in the UK for the sixth straight year, I was thinking exactly this, Tessa! Freeadult porn
Medical clothes include gowns, shoe covers, trousers, shirts, oversleeves, aprons, visitor coats, caps, etc. Sex insult xxx chat for free
Just fuck my ass The humble neck tube is genuinely the Swiss Army Knife of the winter wardrobe. it's useful for everything, and this PX-365 version is the best looking one you can buy. Seamless, hi-stretch polycotton Wear in any of 10 styles Protects against wind and UV. Only 9.99 Found in: Clothing Clothes Headwear More info Planet X Hi-Viz Skull Cap Designed specifically to be worn under cycle helmets. Super thin and light thanks to its hollow core prolen construction this Skull Cap will also increase your visibility on the trail. Only 4.99 Was 9.99 50% off Save 5.00 Found in: Clothing Clothes Headwear More info 2015 Pro Team Cotton Cycling Cap Be one of the team! Only 4.99 Was 12.99 61% off Save 8.00 Found in: Clothing Clothes Headwear More info Clearance El Guapo Baseball Cap 100% cotton baseball caps that will give you authentic American look! Only 1.49 Was 4.99 70% off Save 3.50 Found in: Clothing Clothes Headwear More info Titus Cotton Cycling Cap Good quality 100% cotton cycling caps that will give you the stylish American look! Only 2.99 Was 4.99 40% off Save 2.00 Found in: Clothing Clothes Headwear More info Clearance Titus Baseball Cap A good-quality cycling cap made from cotton with 2 Titus logos so that you can show how much you love this American brand! Only 1.99 Was 4.99 60% off Save 3.00 Found in: Clothing Clothes Headwear More info Clearance Titus Classic Cotton Cycling Cap Good quality 100% cotton cycling caps that will give you the stylish American look! Only 2.49 Was 4.99 50% off Save 2.50 Found in: Clothing Clothes Headwear More info Clearance Titus Winter Beanie A good quality 100% cotton beanie that will make you look stylish when it gets really cold! Only 1.99 Was 4.99 60% off Save 3.00 Found in: Clothing Clothes Headwear More info Clearance Planet X Beanie Show your love for Planet X in style by putting one of these warm and cosy beanie hats on your head. Essential item for Autumn/Winter, or indeed all-year British climate.
You should be a part of a contest for one of the finest websites online. I m going to recommend this web site!
Twilight star gay sex with jonas Fifty years ago, on 18 March 1965, Soviet astronaut Alexei Leonov took the first space walk. Listen to Rob and Neil describing the struggles of that ground-breaking space mission whilst explaining some related vocabulary. Dick in ass porn
We elected to go for sunset because we are staying in Kapalua and did not want to get up at 2am for sunrise. We spent the day visiting other local attractions and headed up about 3pm. It was very cloudy and rainy going up and we had our doubts about if it was worth the trip. We had downloaded the Gypsy App for Haleakala which is a guided audio tour and it reassured us that the weather would be different at the top and it was! Sunny and clear, although the temp went from 80 down to 63 degrees at the top. The Visitors Center at the base is under construction and the one at the top is open from 10-3:30. There are restrooms at the summit. There are many switch backs and driving can be nerve racking but definitely worth the views. Young shemale porn
I WANT A MILLION DOLLARS!!! Can one million RICH WHITE PEOPLE send me one dollar apiece, puh-lease???? wwe divas nude tits
Tits ass porn There are those who combine as well. I see the north face fleece vest over a lot of business casual here in SF and the silicon valley. I think they give you one when you move to the peninsula.
Teen magazines for girls OMG! This is sooo funny! I m in seattle and no one knows how to dress anymore. We make fun of those women who wear velour track suits but is it any better to go to Starbucks all decked out in REI?
Lesbian ass smothering Our after dark cocktail dresses , formal dresses, designer dresses and party dresses are by labels such as Motel, Bless'ed Are The Meek, August Street and Fairground, Toi et Moi. Classic girl american
A lot of North Face stuff is made in Sri Lanka that has one of the worst human rights records on the planet. Ali larter nude sex
They're attracting all the investor interest because each company is trying to fill a void left by the big online retail incumbents. Though Amazon is deeply entrenched in almost every product category in e-commerce, and eBay rules resale, many consider fashion their most vulnerable segment, whether new or used. Amazon and eBay thrive as near-boundless vending machines, where customers search for anything and everything. Fashion is built on meticulous curation. no panties dancing
Juliette lewis ass I agree with Tina. I would think that line drying vs. electric drying would not be enough to cause World War III on Jillee s very eye opening post. It s true that it saves a lot of money when you line dry clothing, but it is not always possible. Please think about things before you type/say them. Pretty blonde girl pictures
Small girl takes big cock Why stop shopping when you can receive free shipping?With a minimum purchase of $50 or more at canada.forever21.com,shipping is no cost to you. This limited time offer applies only tostandard ground shipping.You must purchase a total of $50.00 worth of merchandise onlybefore taxes, shipping and handling. Does not include Forever 21gift card unless purchased with merchandise totaling $50.00 ormore before taxes, shipping and handling. No price adjustments onprevious purchases. Offer is non-transferable without consent byForever 21. Not Valid at Forever 21 or XXI stores. Cannot becombined with any other offers. Valid on regular Canadian shippingonly. Shipping promotions do not apply to orders shipped to Nunavut,Yukon and the Northwest Territories. Additional charges apply forexpress shipping. Junior bridesmaid and flower girl dresses
That side twisty ponytail definitely needs a tutorial to go with it are you listening, Namrata Soni ? Jayden james free porn videos
Furniture Beds Sofas Mattresses Wardrobes Chest Of Drawers Chairs Tables Dining Table & Chair Sets TV Stands Cabinets Cots & Cribs Sofa Beds Headboards Storage Sideboards Bedroom Furniture Sets Bookcases & Shelving Living Room Sets Forbidden love hentai streamariganusaru
You'll never have to hem and haw about whether something will be useful later, whether you should keep it because it's a 'good shirt' or was expensive or any of that! Note that 'sparking joy' applies perfectly well to items that aren't exactly thrilling but that serve us well. For instance, the cotton camisole that doesn't rise up and is just the right length — that sure sparks joy for me! Socks without holes spark a lot more joy than socks with holes. You get the picture. gangbang xxx
For gay marriage debate The highest-quality clothing made in Italy specifically to provide the best performance possible, the Flanders range might be just for you! You will feel comfortable thanks to a sizeable chamois pad and the breathable fabrics. Only 39.99 Was 69.99 42% off Save 30.00 Found in: Clothing Clothes Leggings Tights and Shorts More info Clearance Planet X Classico Bib Short A retro-looking set of Bib Shorts made of the best and most modern fabrics in Italy. It has been designed and tested in racing conditions during long cycling seasons to ensure the best quality and performance possible. Only 39.99 Was 55.99 28% off Save 16.00 Found in: Clothing Clothes Leggings Tights and Shorts More info Clearance Planet X Compression Calf Guard Lower calf compression guard to help increase blood flow during a race and to aid recovery after heavy training. Not bad for cold day or injured legs either.
French lingerie brand If your computer box has important identification material printed on the side, cut that portion from the box or take a photo. The only valid reason to keep tech boxes is if you frequently upgrade your devices and sell your used items. In that case, keeping the original packaging will probably increase their value. Nice pussy tits Portia de rossi naked
What about non-white people who wear technical clothing eh? I m 1/2 yellow and 1/2 white and I wear a ridiculous amount of technical clothing. Although I always want to go camping, I m not so stupid as to think my buddy s going to call an impromptu session of hiking and paddling. I for one wear technical clothing because I m a paranoid bastard. When those zombies come, you want to be hunkered down in a makeshift shanty dressed in cotton, that retains water and chills you when the temperature drops? I think I ll stick with my technical clothing. I may look like a douche, but damn yo, how many hipsters look like douches and are just gonna be eaten by zombies because they can t run in their drainpipe jeans? Sheeit yo, it ain t just white people wearing clothing that works, that in itself is degrading to people of other shades. What, because I m 1/2 Chinese I can t be (paranoia-fuelled) practical? C mon!! Portia de rossi naked Nice pussy tits


text:
NFC Times Exclusive – While Apple is believed to have offered Chinese financial institutions a price break on the cut of transaction fees it demands for participating in Apple Pay, the tech giant doesn't appear to have extended the same offer to banks in some other countries.
Banking sources in Canada and Australia told NFC Times that Apple has not come down significantly in the size of the cut of transaction fees it is asking for. That is despite months of resistance by major banks in these two contactless card payment hotspots.
In Canada, a banking source said Apple's asking price is still not much lower than what it is collecting in the U.S. from issuers participating in Apple Pay, which is 15 basis points or .15% on the amount of credit card transactions, and half a U.S. cent on debit card transactions. Interchange, however, is generally lower in Canada than in the U.S.
Get access to all premium content and the world's first global newsletter devoted to the NFC and contactless markets by subscribing to NFC Times, the most authoritative source for news and analysis in the industry.
Subscription Options
If you already have a subscription, log in here.
NFC TIMES Exclusive Insight – Vivo, China's second largest smartphone maker, made it official this week, launching its NFC-enabled "vivo Pay" wallet, the last of the major Chinese phone OEMs to roll out NFC payments–though their use has been disappointing, at least for payments in stores.
NFC TIMES Exclusive Insight – Given the poor financial results of U.S.-based Fit Pay, it's becoming clear that the business case for provisioning of payment cards to wearable devices remains difficult.
NFC TIMES Exclusive Insight – Plans disclosed this week by JPMorgan Chase to shut down its Chase Pay app for in-store purchases is yet another nail in the coffin–perhaps the final one–for bank wallets in the U.S. And the situation does not look much brighter for bank-issued wallets abroad.
NFC TIMES Exclusive Insight – Transit officials in Miami-Dade County, Fla. are the latest in the U.S. to introduce open-loop payments of fares with contactless credit and debit cards and bank card credentials on NFC wallets, launching the service yesterday on the city's relatively small metro network, with plans to expand to buses later.
NFC TIMES Exclusive – Transport for Greater Manchester, which last month launched open-loop payments on its large Metrolink tram network, said Thursday that contactless credit and debit cards and NFC wallets accounted for a combined 170,000 rides during the first four weeks of the service.
NFC TIMES Exclusive – When New York City transit officials announced Tuesday that the 1 millionth ride paid for through their new OMNY open-loop payments service had arrived ahead of schedule, they also proudly noted that 80% of the contactless payments had come from NFC wallets, not physical bank cards.
NFC TIMES Exclusive Insight – As Japan continues to fight what to date has been a losing battle against cash, an announcement by the joint venture behind QR code-based payments service PayPay offers a little bit of encouragement.
NFC TIMES Exclusive Insight – As Apple Pay approaches the fifth anniversary of its launch in the U.S., there is more research showing that most American consumers simply don't see the value of tapping to pay with NFC-based payments services.
NFC TIMES Exclusive Insight – Five years ago next month, Transport for London introduced open-loop contactless payments across its transit network, including metro, trams and commuter rail, following an earlier launch on buses. The service now accounts for more than half of all pay-as-you-go journeys and has become a global showcase for the technology.
NFC TIMES Exclusive Insight – While noting to financial analysts late Tuesday that Apple Pay is now approaching 1 billion transactions per month globally and is in 47 markets, perhaps Apple CEO Tim Cook's most significant comments about Apple Pay this week was to again emphasize that Apple wants to enable users to routinely tap to pay for bus, subway and other transit rides with their iPhones and Apple Watches.
NFC TIMES Exclusive Insight – China's mega-mobile wallet providers have continued their rollouts of transit payments in China, with Tencent Holdings announcing Tuesday that two years after launching its first QR-code-based WeChat "Ride Code" service in Guangzhou, total users for its transit payments services has reached 100 million.
NFC TIMES Exclusive Insight – Transport for New South Wales, Australia, the authority that oversees transit in and around Sydney, has taken a step toward phasing out its closed-loop contactless Opal fare card, today extending nearly all of the discounts it offers on Opal to users of open-loop Visa- Mastercard- and American Express-branded contactless cards.

subset: commoncrawl


text:
I have had mixed experiences with knit uppers. My first one was with the Nike Flyknit Trainer, which took a significant amount of skin off my achilles area. I had some success with Skechers knit uppers (great with the Ride 7, not so good with the GOrun 6). Mizuno tends to either be the OG or waits to get things done right. They had one of the original minimalist shoes in my opinion, the Mizuno Wave Universe, but never called it that. Slowly they have begun to lower the heel drop of some of their shoes like the Wave Shadow (8mm). Now they have decided to go after the knit uppers. These can be seen in the Waveknit R1, which is essentially a knit upper on the Wave Rider sole and the S1, a knit upper on the Wave Sky sole. Given my preference for lighter shoes, Mizuno was nice enough to send me the Waveknit R1. I am impressed that Mizuno has done their homework and this is by far my favorite knit shoe to date and the only one I have been able to wear sockless without issue. So let's talk.
Specifications (per Running Warehouse)
Weight: 10.3 oz
Stack Height: 30mm/18mm
Drop: 12mm
Classification: Neutral Trainer (with Knit Upper)
The Waveknit upper provides a snug but comfortable fit. The heel is especially snug due to a high level of cushioning in the upper. This opens up into more room in midfoot and forefoot. The fit of the Waveknit R1 is very different from the Wave Rider, which is traditionally higher volume.
The Waveknit weave is fairly thick. This is not thin Nike Flyknit. The upper is still very thick and durable provides a snug fit to lock down the foot. This thickness increases the hold on the foot and this is one of the first knit shoes I can go around corners without my foot slipping off the platform. This is especially apparent as mentioned in the heel with the amount of padding and cushioning around there. There is a heel counter back there, but I cannot feel it at all due to the cushioning and I have had absolutely no irritation of my calcaneus (heel bone). Which is extremely rare for a shoe that I have worn so much sockless.
The sizing is very true to size. Many will be fine wearing socks in this shoe and there will be enough room (although snug). I found wearing my normal size 10 with and without socks just fine. With thicker socks it almost feels like a compression like fit (which some may enjoy).
I found plenty of comfortable room wearing these shoes sockless. I do not know if this is from the high number of miles I have put on my feet (and the skin toughness), but I found the against skin comfort incredibly high. This is one of the first shoes I have been able to take sockless above 10 miles without the fear of blisters. My longest sockless run was 14 miles and while my legs were a bit trashed due to doing this at 5am, I had no issues. I believe I have said that shoes "disappear on my feet" before. This one actually does and I have to take back that comment from others.
Another surprise from the upper is that these breath very well. I was expecting the thicker upper to get very hot, but there is plenty of ventilation to keep the foot cool. It is certainly not the most ventilated shoe, but I have had no issues running sockless in +80 degree Southern California weather.
The sole of the Waveknit R1 is firmer as typical Mizuno go but slightly softer than Rider 21. I do not know if this is from the upper, but it feels much lighter than 10.3 oz weight. I have used these for long runs, steady state runs and fartleks without issue. I do need a little more stability than the Neutral Wave Rider sole, but for picking up the pace a little these shoes are great for me. There is a bit more inherent stability due to wave plate and firmer ride, but I still need a bit more on easy runs.
The ride of the sole is very smooth. With the Smooth Ride tech (gender specific flexibility), flexibility seems to be placed in all the right places in the forefoot. Combined with some toe spring, toe off is smooth and seems to unload the calves a little. The heel and midfoot are somewhat stiff, but thanks to the wave plate and a correctly place posterolateral heel bevel (which helps with forward transitions), the ride is smooth. The heel bevel and wave plate make for extremely smooth heel landings.
While this is a traditional 12mm drop shoe, I have never really felt the heel got in the way. I will fully admit that I tend to land higher back, but when the pace picks up, landing further forward feels fine. Many shoes with most of their cushioning tech in the heel feel very unbalanced. Mizuno seems to do a better job of evening this out despite the wave plate being all in the heel. This might also be due to the fact that the wave plate takes up less weight and the width of the forefoot tends to be wider (thus may make a more stable landing). Thus the 12mm measurement is likely inaccurate and may be far lower when the midsole is under load. Dynamically loaded and static stack heights are different! Would I complain about the drop being lowered a bit to 8-10mm? No, and that is already starting to happen in a few of their other trainers (Shadow, Sky, Horizon).
As mentioned previously, the Waveknit R1 feel lighter than they actually are. These are trainers, but they can handle fartleks, strides, hill repeats and uptempo runs. They are responsive when the pace picks up, but I would choose a far lighter shoe for most workouts or races (check out my review of the Mizuno Wave Emperor 3). For those looking for additional protection over the marathon distance, these would be a great shoe as it does feel lighter and does have some bounce to it from the firmer sole and wave plate. However there are far lighter and faster shoes out there. This is a trainer after all.
As with most trainers, particularly from Mizuno, the durability is fantastic. I have not seen any fraying of the upper or major sole wear after almost 80 miles. I expect to get many hundreds of miles out of these and will even retire them as casual shoes because I expect the wave plate and upper to hold on for quite some time.
The knit uppers are just the beginning of a new era of custom fit shoes. The fit of running shoes are based on what is called a last (shoe shape). Some companies may use the average shape of a group of professional and recreational runners to develop the last to reach a broader audience. Others may just use the foot shapes of their elite runners. As a customer, you are always trying to find the last that fits your foot best. With the onset of knit uppers, the shoes are fitting better to people's feet because they stretch and accommodate variations better. People do NOT have the same shape or size feet. Men and women have differently shaped feet (arch lengths, widths, etc), different people have different shaped feet, different cultures have different shaped feet. Just look at the shoes in the Asian vs the US market. There is a reason there is a wide version available of every shoe INCLUDING racing flats in Asia! However, the next step is to have not only the upper, but the sole customized to the foot. Imagine having flex points, plates, posting, stability and more customized to your foots preferred motion path?
The Waveknit R1 is a shoe with a knit upper done right. It is thick enough to provide durability and a good lock down of the foot while being very comfortable with or without socks. The ride is similar for those who love the Wave Rider series, providing a lighter traditional trainer that can still handle some uptempo training. I really hope Mizuno does more with the knit uppers as I think they hit a nice balance between keeping the foot comfortable and locking it down on the platform. Plus I am still impressed I was able to run 14 miles sockless in this shoe. So definitely give these a try, if for no other reason than to see how comfortable that upper is!
Thanks for reading!
Doctor of Physical Therapy
Kaiser SoCal Manual Therapy and Sport Fellow


text:
The yarn I used came in short lengths and I had to tie it in the back and start again from where I left off. If I made these flip flops again, I would definitely use one length of yarn.
Death Note
*If you don't know "Death Note," you should.*
I used black card stock with white paper and I sewed the pages together with black string. Inside I attached a printed copy of the rules. The "Death Note" title is actually painted on. I'm not good enough to do it by hand, so I found a Ryuk handwriting font, printed the words, and cut them out to make a stencil.


text:
GHS (GHS) Class of 1988 Alumni List
Help us Update the GHS 1988 Class List by adding any names missing from the list below:
Registered Alumni
1988 Class List
Know GHS Class of 1988 graduates that are NOT on this List? Help us Update the 1988 Class List by adding missing names.
Rain Man was the top movie in theaters in 1988, with a lifetime gross of over $172,825,435. Among TV shows in 1988, The Cosby Show was the most popular of the year.
Hit Songs From 1988
Shattered DreamsJohnny Hates Jazz
Cherry BombJohn Cougar Mellancamp
Need You TonightINXS
Make Me Lose ControlEric Carnen
If It Isn't LoveNew Edition
Just Like ParadiseDavid Lee Roth
One Moment In TimeWhitney Houston
Man In The MirrorMichael Jackson
Get Outta My Dreams, Get Into My CarBilly Ocean
1 2 3 4Gloria Estefan and Miami Sound Machine
Hit Movies From 1988
Hit TV Shows From 1988
Reunions and Germantown High School News
More 1988 alumni from Germantown HS Germantown, OH have posted profiles on Classmates.com®. Click here to register for free at Classmates.com® and view other 1988 alumni.
Missing some friends from Germantown High that graduated with you in 1988? Check the list below that shows the Germantown Germantown, OH class of '88.
Don't forget to upload your Germantown High School pictures and check on the latest info about any Germantown High School reunion.


text:
8.0pretty bad
- Typical Repair Cost:
- No data
- Average Mileage:
- 25,000 miles
- Total Complaints:
- 1 complaints
Most common solutions:
- not sure (1 reports)
problem #1
May 052018
Stinger GT 3.3L V6 Tt
- Automatic transmission
- 25,000 miles
Continued problems with the paint of my Micro Blue 2018 Kia Stinger 2018. KMA has terminated any and all requests to have these problems fixed, caused by paint from the factory, and a horrible re-paint shop that was chosen by KMA. KMA will not work with me, and continues to say that all of these problems are rock chips. Car paint continues to deteriorate. KMA had a stop-sale of all yellow and blue Stingers for a period of time, then came out say that all Yellows had issues, and allowed for buy-back or complete repaints of that color. (Very limited 400 yellow cars) Blue Stingers stop-sales were lifted, with no way for the owners to have the same exact problems fixed.
- Matt R., Phoenix, US


text:
Cerise grabbed her lunch and ran to the student council room, hoping to find Sarah. Sure enough, the Green Girls were preparing posters to be placed above the recycling bins, hoping to discourage students from using the bins as garbage cans.
"Hey Cerise," said Sarah, letting her into the room.
"Terry totally just asked me out!"
"Oh my god!" Sarah, Mel and Steph all screeched at once, causing a small sonic boom to ripple out of the school.
"We're going to Clydes on Halloween! And he kissed me!"
"Oh my god!" Mel exclaimed.
"What was it like?" asked Steph.
"Amazing! He has like, oh my god, the softest lips!"
"Oh my god," the Green Girls swooned.
"He actually smelled a bit like cigarettes, which was gross, but maybe that was just the residual stench from Porta-potty chick, she was totally smoking in the girls' bathroom, and I mean, like in a serious way. It reeked of pot and like the smoke was so thick I could barely even see past my own hand."
"She's so rank," sneered Mel.
"Totally," agreed Steph.
"So should I wear a costume?"
"What do you mean? Like for your date?" asked Sarah.
"Yeah, 'cause it's Halloween."
"No," Sarah shook her head. "I've never seen Terry wear a costume, like not even in Sec 1. None of them do."
"Yeah," Mel and Steph nodded.
"Kinda boring. I like dressing up for Halloween," shrugged Sarah.
"Me too," admitted Cerise. "But ok then, what should I wear?"
"Do you own any skirts?" wondered Sarah.
"Not really."
"I could lend you one," Sarah offered.
"Like they'd fit," Cerise surveyed Sarah's body. "You're way skinnier than me."
"Aww, not really." Sarah smiled.
"Yeah, way. But that's ok, I can borrow a skirt from my sister, Simone. And she has like a hoodie that's black and purple checkered and like, I guess I could wear my converse and leggings?"
"Sounds good," Sarah approved while Mel and Steph nodded in agreement.
Cerise was forced to do the run after school to make up for ditching the boys at lunch. Once the task was completed she joined them as they walked to Jay's house.
"So you coming to my place for Halloween?" Jay asked.
"Yeah, we do a thing every year."
"Oh well…" Cerise shrugged. "I kinda have plans on Halloween."
"With Sarah and her clones?" asked Karl.
"You gonna try to do something with Porta-potty chick?" wondered Jay.
"You're gonna hang with the Asgard? The Tok'ra? The Knox? Oooh, the Furlings!" Vani hopped around from foot to foot as they climbed the overpass.
"I'm just doing… stuff."
"Like…" Jay prompted.
"Like I can't do stuff without getting you guys' permission first?"
"Are you like, gonna have a pillow fight in your underwear but instead of a pillow you're gonna use a whip and instead of your underwear you're gonna be in a dominatrix outfit?"
They all stared at Willy.
"No," Cerise said with a glare. "And gross." She was about to swing out her hand to smack Willy but thought better of it, not wanting to encourage him. "I'm gonna go out with Terry."
"What?" They all screamed.
Jay was livid. "Terry Trebifucktard!? You are not!"
"God, whatever," Cerise rolled her eyes.
"In what context are you gonna go out with Terry Shitforbrainsky?"
"In the context of doing stuff."
"You're gonna go out with him? Like go out? Like out, out. Like, to go out. Like, as in the opposite of in," Jay fumed.
"I see you've mastered the definition of out."
"Mmhhmmph," Karl clucked his tongue and shook his head in disapproval.
"Wow, you're dating Terry Trebichavsky? That's pretty cool," said Vani.
This comment was rewarded with various punches to the chest, arms and even an attempted kick to the groin, but Vani was scrappy and managed to avoid injury.
"Well it's not like we're dating. It's just a group thing at a pool hall."
"Next think we know you're gonna start smoking," Karl smirked.
"Oh, I will not."
It was a good point though. Terry was a smoker, which was totally gross. Cerise had always believed that smoking was a dealbreaker and
never would have imagined going out with someone who ulged in such a disgusting habit but that was before Terry had kissed her with his amazing lips of awesomeness. ind
It was only after a long and painful session of gaming, wherein Vani conquered a planet of Wraith worshippers and Willy fell asleep in his own drool that Cerise went home and the boys were able to discuss the situation honestly.
"Life is so easy for girls," mused Vani. "I mean she lusted after a guy and then she actually got him. That's insane!"
Willy was finally roused from his slumber. "She's gone to the dark side. I knew it."
"It was inevitable," shrugged Karl. "She was too attractive to be hanging out with us."
"Yeah, I guess so," sulked Willy.
"Are you really surprised?" asked Karl. "You had to know she wasn't gonna start going out with one of you losers."
Willy picked at the stuffing that was poking out from a couch cushion. "Sucks. She was cool. And hot."
"It was fun while it lasted," said Vani. "What do you think? Bajoran death chant? Klingon death scream? Old school bagpipes?"
"It's not like she's gonna stop hanging out with us altogether!" Jay insisted.
"Wake up Jay-dalee-a-son! If she's going out with Terry-I can crush liger skulls with my bare hands-Trebichavsky then there's really no way to get around it," said Vani.
Karl nodded in agreement. "You can't go out with Terry Trebichavsky and hang out with us. You just can't."
"She's not gonna stop hanging out with us," said Jay with a little less confidence.
"Yeah right," whined Willy. "She's probably sucking his cock right now!"
"Ugh!" Karl gagged. "Don't say words!" He smacked Willy's face with his Rifts manual.
Suddenly Vani jumped up and grabbed Jay's shoulders. "Does this mean she's not gonna be in the elephant?"


text:
Basic Information
- About Me
i smoke i smoke i smoke...and i smoke.
overall im the jolly ol party party party lets all get wasted. normal teenager you catch on the daily.
wiz khalifa is amazing as if you didnt already know..
& this is my outlook on life "We cry when we're born, n' we cry when we die...
So in for the time in between... I'ma enjoy life
- Sex
- Female
- Member for
- 8 years 31 weeks


text:
Ruth Davis is a junior research fellow in international economics at Chatham House.
This site uses cookies to provide the best online experience. By using this
site, you agree to the use of cookies and collection of personal information per our
Privacy Notice. To alter or disable the use of cookies,
adjust your browser settings.


text:
College of Engineering
College of Design & Sports
College of Humanities & Social Sciences
College of Health Science
Graduate School
Graduate School of Industry & Science
Graduate School of Disaster Prevention
:: Divisions and Departments ::
Department of Food & Nutrition
Department of Herbal Medicine Resource
Department of Broadcasting Visual Media and Technology
Department of Emergency Medical Services
Department of Nursing
Department of Physical Therapy
Department of Radiological science
Department of Optometry
Department of Dental Hygiene
Department of Occupational Therapy
The Department fosters occupational therapists to help those people with physical/psychological problems to be independent through doing various activities. The activities include daily actions such as wearing clothes, eating meals and social activities such as typing keyboards, counseling customers, and piling up boxes.
The goal of the Department is to foster a competent occupational therapist to have a cool head and a warm heart with the concept of whole person education for the society.
1. Thank to the society and the parents
2. Foster responsible and healthy professions
3. Have a volunteer spirit and love nature & human beings
4. Pursue development of occupational therapy and play a key role in it
To achieve those goals, The Department of Occupational Therapy in Kangwon University.
- Medical Institute (university hospital, general hospital, rehabilitation hospital, sanatorium, psychiatric hospital)
- Special-Education School (specially trained teacher)
- Rehabilitation & Welfare Field (welfare center for the disabled/senior, welfare center, rehabilitation center, day care center for disabled children)
- Business (job training center, medical appliances company, health care centers in a company)
- Professor & researcher
- Occupational therapist
- Ergonomics Engineer
- Rehabilitation Assistant
- Health Education Instructor


text:
Lawrence Education Center presented 177 diplomas to graduates on Friday, June 3, 2011, at Springfield Southeast High School Auditorium. Ninety-nine (99) students received high school diplomas and seventy-eight (78) received their GED certificate.
Several graduates were the featured speakers at graduation.
The following awards were presented during the evening:
Matilda McLaren Award - Mrs. Matilda McLaren was a teacher and advocate of adult education. She worked tirelessly to help people prepare for retirement; immigrants to gain the skills they need for citizenship and helped married mothers escape their destiny of dishes and diapers. She was outstanding in providing services to adults in most need.
Rob Mehan works in the Investor Education Section of the Illinois Securities Department at the Illinois Secretary of State's office. He provides financial workshops for the population at LEC.
Peg Stroh Scholarship �" Established in memory of Peg Stroh who for many years was a guidance dean at Lawrence Education Center.
Patrick Uhrich— plans to pursue a career in the medical field so that he can help people and make a difference.
Victory in Education Scholarship was established by an anonymous benefactor for graduating students who plan to enroll in a college or trade school.
Chante Hardy plans to pursue a career in teaching.
Daisy Capeles plans to pursue a career as a dental assistant.
Prepare Youth to Work Employed Student of the Year was established to recognize a student who has shown growth in the world of work and continues to be employed.
Laci Rebbe worked at SCOPE Daycare and has gained xperience in childcare. Laci's goal is to own and manage a daycare. She plans to attend college to earn a degree in early childhood education.
Troy Johnson Volunteer of the Year Award was established in memory of Troy Johnson who served for many years as a volunteer at Lawrence Education Center.
Bonnie Schukai volunteers daily in the English As a Second Language program and assists students with preparing for jobs in the community.
Kathy Handy volunteers daily in the English As a Second Language program and assists students with American
culture and community awareness.
Key to Our Success was established in 2010 to recognize individuals from the community that exemplify the key to adult education success.
Two Recipients were announced:
Chuck Hoots and Katie Rasmussen


text:
Post Top Ad
Thursday, 1 March 2018
40-year-old France President Emmanuel Macron steps out with his 64-year-old wife, the internet goes crazy
About Ebalsblog
3 comments:
- Charles Christian said...
thanks… I've been bookmarking them for a while now and just decided to create a post to provide them to others… I would like to hardly recommend you to visit nexter org this blog for more news updates !!
- 9 October 2018 at 09:56
- Bradley Copper said...
My girlfriend has been cheating on me for months and I had no idea, I searched online to get help spying her iphone. I finally found a recommendation post about a reliable PI to help and I strongly recommend firstname.lastname@example.com or whatsApp : +12678773020 Mr James to anyone who needs help spying their partner. I was able to access her iphone contents remotely and It literally worked . Don't hesitate to message him if you need help, i enjoyed his services.
- 9 December 2018 at 04:30
- fram said...
Hello my dear viewers,i will say to the world to celebrate with me on this numerous testimony, i never believe i could ever get rid of this horrible disease until one fateful day,my story and appreciation goes to Dr. Afrid the powerful great doctor that help me to cure my HIV/AIDS disease from my life,he is truly a truthful man with high herbs power's he uses on saving people's life, just a few days back i came in contact with Dr. Afrid emails which many individuals have testify so much about of his kind work, so i decided and contacted him quickly because the disease was almost at the last minute of taking my life, i have tried all remedies from several physicians from hospitals but none could help me apart from Dr. Afrid who finally cure my HIV/AIDS disease, i was amazed and overwhelmed when the doctor confirmed me negative in the same hospital i have been before,i wish to anyone that is sick today and want healing to please contact this doctor (email@example.com) so if you have any problem HIV, HERPES, CANCER, ALS,HEPATITIS B, DIABETIC,or call/whatsapp him +2349057260738. thanks sir.
- 17 July 2019 at 09:23


text:
ROCKY POINT, NC (WWAY) — Pender County Utilities water customers along Lightwood Knot Road in Rocky Point are advised that due to a leak Sunday morning, water was temporarily turned off to conduct a water main repair.
Water service was returned upon completion of the work, but periods of low or no pressure in the distribution system increases the potential for back siphonage and introduction of bacteria into the water system.
"Consumers are advised to boil all water used for human consumption (including drinking, making ice, brushing teeth, washing dishes and food preparation) or use bottled water until this advisory is lifted," said Kenny Keel, Pender County Utilities director. "This advisory will be in effect for a minimum of 24 hours."
Vigorous boiling for one minute should kill any disease-causing organisms that may be present in the water.
Water customers are strongly urged to conserve water whenever possible.
This advisory remains in effect until further notice.


text:
Upcoming Fire Safety Classes
At The Floasis, 1342 Dekalb Ave Brooklyn NY
Part 1: $50@ The Floasis 1342 Dekalb Ave Brooklyn NY
Part 2: $35 @The Floasis 1342 Dekalb Ave Brooklyn NY
Upcoming Fire Safety Classes
At The Floasis, 1342 Dekalb Ave Brooklyn NY
Part 1: $50@ The Floasis 1342 Dekalb Ave Brooklyn NY
Part 2: $35 @The Floasis 1342 Dekalb Ave Brooklyn NY
No RSVP or registration necessary (just show up on time!) you can pay in person via cash, Paypal or Venmo.This is a two part class that is excellent for all skill levels.
The Floasis holds fire performance safety classes that are accepted by the FDNY as a prerequisite to the E29 Fire Performer COF. To learn more about NYC requirements for fire performers visit https://thefloasis.com/fdny-faq
There are opportunities at the end of Class 1 or Class 2 to audition for a letter of recommendation. Class 1- 5 hours $50 practical fire performance safety course
Class 2- 3 hours $35 How to get certified with the FDNY
Class 1 is so full of information, everyone will learn something. If you have never touched fire before ~or~ have been doing it for years, you will find value in taking this class. When you finish class 1, you will receive a Certificate of Completion that is accepted by the FDNY (one document needed for the E29 COF, visit https://thefloasis.com/become-licensed for the entire list). Class 2 is not required by the FDNY but it is very helpful for professionals performing with fire in NYC to understand the regulations.
What to bring: Clothing suitable for outdoors, paper and pen.If you want a letter of recommendation for the E29: bring your props, buckets and wear something appropriate to perform fire in.The Floasis can not issue Certificates of Fitness (eg CoFs E-29, F03/F04). The FDNY is the only organization that can test for and issue CoF's. Our safety course is one of two options accepted by the FDNY as one of requirements for the E-29 CoF. The other safety class can be found online here: https://flowartsinstitute.com/product/fai-fire-safety-course/
Class 2 focuses on License, Permits and insurance requirements. We will go into indoor fire spinning, how the test works and how the inspectors operate. This class is a lecture about how to legally perform with fire in NYC. We go over licensing, how to make and appointment and what to expect on the test. We also go over permitting, how to file for one and how to make venues safe. We also go over insurance and equipment requirements and where to find them. This class is not accredited by the FDNY and does not guarantee a letter of recommendation or a COF. More info on FDNY performance regulations can be found here https://thefloasis.com/fdny-faq


text:
Separate names with a comma.
I'm looking for beta testers to help final balancing of OCO - a one-touch puzzle platformer for iOS and Android. It's due for release...
Link: https://itunes.apple.com/us/app/endless-archery/id1390437916
Endless Archery
Endless Archery is my upcoming arcade archery game, releasing November 14 for iPhone! It's a mashup between an...
Hi All !
I'm here to post the very first informations about an upcoming title we are working on, Eagle Life (name not yet definitive, open to...
Happy to introduce the soon coming RC Plane Explorer (title still temporary, open to suggestions).
We have been hard at work to complete a...


text:
Title Search
Advanced Search
Current News
Specialty Items
Site Features
About Us
Back to Page Top
GREEN LANTERN (1960) (#1-224) (DC) #40 - Bibliography
What could turn these two allies, fellow crusaders in pursuit of
intergalactic peace, on each other? Nothing less than a secret so deadly, so
potent, that its revelation could spell the end of all existence. At the
behest of the powerful Guardians of Oa, Green Lantern must dual Green
Lantern for the fate of the universe.
If you read Crisis on Infinite Earths or you want to know more about the
very origins of the DC Universe and the Guardians of Oa, this is your comic.
Here, embellished by the dramatic plot of John Broome and the graceful
pencils of the late, great Gil Kane, is revealed the terrible consequences
of a quest for knowledge gone horribly wrong and the events that led up to
the creation of the Green Lantern Corps itself.
Title: The Secret Origin of the Guardians
Featuring: Green Lantern
Character Appearances: Green Lantern [Hal Jordan]; Green Lantern [Alan Scott]; Krona (intro)
Credits: John Broome (Script), Gil Kane (Pencils), Sid Greene (Inks).
Return to Title Search
View all issues of this title
Prices in boldface BLUE are for items shown as in stock (subject to prior sale...).
Prices in boldface GREEN are for items that are presently onSale.
Prices in boldface RED are for items that are presently being discounted from normal price (this changes daily!).
Prices in boldface YELLOW are for items that are on sale as a result of a genre sale that was announced via our weekly e-mail newsletter.
Privacy Policy: Mile High Comics, Inc. does not share any of your information with anyone.
Website Programming by ii, inc.
Captain Woodchuck and all data © 1997-2018 Mile High Comics, Inc.TM All Rights Reserved.
Mile High Comics is a registered trademark of Mile High Comics, Inc.TM All Rights Reserved.


text:
When you need Marrero auto care to get your car through the winter, call on the Marrero auto care gurus at Twin Tire.
It's holiday time and a lot of people are planning road trips to be with distant family or friends for the season. Others are planning a seasonal getaway to, well, just get away. Still others are planning to stick around Marrero whether it's to stay home or enjoy one of the many activities around the city from the Celebration in the Oaks to Jingle on the Boulevard.
Travelers and stick-around-towners have something in common – the well being of their cars. Neither one wants their car to have trouble at any time, but particularly not during cold winter holiday time.
There's a way to help prevent a breakdown. Just make sure you keep up with routine auto care and, as State Farm Insurance suggests, add in some steps because it's winter:
- Check tire pressure weekly. Driving on underinflated tires can cause them to wear down prematurely and lose traction on icy or rain slick surfaces. Your tires lose a pound of pressure with every 10-degree drop in temperature.
- Keep your fuel tank half full. During winter weather, it's a good idea to keep at least half a tank of fuel in the vehicle in the event of an emergency or if you get stuck and need to wait for rescue. For longer road trips, plan stops for gas in advance.
- Add a protective layer. A coat of polymer wax can create a barrier against road salt, grime, sleet, mud and more. Couple that with high-pressure car washes after winter storms to rinse away buildup in hard-to-reach areas such as wheels, wheel wells and underbody.
- Protect your windshield wipers. If you park outdoors in freezing weather, leave the wipers in the raised position to prevent them from freezing to the windshield. Never use your wiper blades to remove ice or frost from the windshield; use an ice scraper instead.
The easiest way to do this is to have the Marrero auto care pros at Twin Tire Auto Care do the work for you.
Twin Tire has been the trusted New Orleans auto care and auto repair service center since 1973. Twin Tire has three convenient New Orleans auto care and auto repair service centers to help you - Marrero, Harvey and Hammond. Twin Tire also has a New Orleans auto repair and auto care location in Harahan for heavy commercial vehicles.
Twin Tire and Auto Care is a proud provider of Firestone Tires | Bridgestone Tires | Goodyear Tires for the New Orleans area.
New Orleans Auto Care | New Orleans Auto Repair | Marrero Auto Care | Twin Tire Auto Care
#NewOrleansAutoCare #NewOrleansAutoRepair # MarreroAutoCare #TwinTireAutoCare


text:
The water hasn't cooled as of yet in Kim Kardashian using the name of another product as the name of her new business, and now Kylie Jenner is being slammed for biting Rihanna's style. Kylie Jenner was bashed when she shot up an image of herself in a $695 leopard print catsuit to promote her cosmetics summer line collection.
Not too long after Kylie shot up the image of herself on the leopard get-up- the energy no woman wants after getting all done up Kylie quickly felt. The memo was sent by social media crazies that Rihanna wore the same outfit, and before Kylie. The cosmetics businesswoman was then accused of biting Rihanna's style. Here we just a few of Twitter users giving it to Kylie:
Then another had this to say:


text:
Click Image for Gallery
An excellent environmentally friendly product at a fantastic price. A pallet of 3600 size AR5 (E/2 equivalent) Arofol branded gold padded bubble envelopes. These are equivalent to mail lite/feather-post size E and jiffy aircraft size JL2. The internal measurements of each envelope are 220mm x 265mm. Classed by Royal Mail as 'Large Letter' size. Arofol branded bubble envelopes are manufactured in the UK from excellent quality FSC paper, which is sourced from sustainable forests. The inside is lined with high quality bubble film. There is also a continuous 10mm edge around the envelopes, for optimal tear resistance.


text:
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ~2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87×10−9; odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10−9; odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
Bipolar disorder (BD) is a common, chronic, and episodic mental disorder characterized by disruptive oscillations of mood and behavior. The lifetime prevalence estimate in the US population is about 2% (BD-I and BD-II), but exceeds 2% for sub-threshold conditions (1, 2). The elevated morbidity and mortality associated with BD make it a major public health problem. Despite advances in recent years, the underlying neurobiology of BD remains largely unknown.
The overall heritability of BD has been estimated to be more than 70% based on twin studies (3, 4). Genome-wide association studies (GWAS) have identified several risk loci. These include markers near ADCY2, ANK3, CACNA1C, TENM4, SYNE1, TRANK1, and a tight cluster of genes on chromosome 3p21, among others (5-9). These loci account for only a small portion of the heritability of BD, suggesting that additional risk loci remain to be discovered.
The highly polygenic architecture of BD (10) suggests that identification of additional risk loci will require larger samples than have been studied so far. As the diagnosis of BD can be challenging, great care must be taken in the selection of cases (11). Accordingly, the ascertainment of well-characterized cases has proven to be a limiting factor. To address this problem, we augment previously published case sets with a large set of well-characterized cases followed on lithium for at least 6 months and assembled by the Consortium on Lithium Genetics (ConLiGen) (12, 13). These cases were included in a recently published GWAS of lithium response (13), but have heretofore not been used for GWAS of BD itself. Since an excess of controls beyond the traditional 1:1 case:control ratio can confer a meaningful increase in power in GWAS (14-16), we have also included over twenty thousand genotyped controls drawn from public databases. Most have not, to our knowledge, been included in previous GWAS of BD.
Surprisingly few of the published GWAS of BD have reported results for X chromosome markers, even though family and genetic linkage studies have long suggested a role for X-linked genes in BD (17-19). While the smaller effective sample size of X-linked markers necessarily leads to reduced power relative to autosomal markers (20), omission of the X-chromosome represents a considerable loss of potential association signals, since it comprises approximately 5% of the female and 2.5% of the male genome. One reason for the omission may be the relative paucity of association methods that correctly account for the added complexities of X-linked markers. Recent advances have improved the available analytic tools (21, 22), and we employ one such tool in the present study. We also employ a large X-chromosome imputation reference panel from the 1000 Genomes Project (23) that was not available during the first generation of GWAS.
In summary, the present study aimed to identify additional BD risk loci by carrying out a GWAS with new cases, excess controls, and analytic methods optimized for the X-chromosome. The most significant SNPs were tested for association in an independent replication sample of about 2,300 cases and 3,500 controls from two independent GWAS studies of BD. While we did not detect any genome-wide significant variants on chromosome X, we did find genome-wide significant evidence for common risk variants at two novel and four known autosomal loci. The results add to a growing list of common autosomal markers associated with BD and demonstrate the power of well-characterized cases, combined with an excess of controls, to identify previously unknown loci involved in common, polygenic disorders.
A total of 7,647 cases and 27,303 controls were analyzed in Stage 1 (Table 1), in which a total of 9,692,718 autosomal markers passed quality control. The p-value distributions were unbiased for each of the sub-studies: all standardized genome-wide inflation factors (λ1000) were ≤ 1.07 (Figure S1). Meta-analysis of the Stage 1 studies identified 62 variants that exceeded the standard genome-wide significance threshold (Table S1). All lie within two known risk loci.7,9 One SNP (rs9834970, P = 3.19 × 10−8, OR = 0.88) lies near the gene TRANK1; all others are located in the gene MAD1L1. All 179 variants with fixed-effect P < 10−6were carried forward to the Stage 2 samples for further validation (Table S1). After LD-pruning at r2=0.2, these results appeared to represent 14 distinct regions,
Meta-analysis of the combined Stage 1 and Stage 2 studies, comprising 9,784 cases and 30,471 controls, produced an unbiased distribution of p-values (Figures S2). The genome-wide inflation factor was 1.08. The standardized genomic inflation factor (λ1000) was ~1.01.
Six autosomal loci exceeded genome-wide significance (Figure 1). Four of these loci have been described before (Figure S3) (7-9, 24). The remaining two loci are novel BD risk loci (Figure 2). None of the six genome-wide significant loci identified here demonstrated significant heterogeneity in effect sizes across the samples studied (Table 2).
The first novel locus is located on chromosome 17q12. The most significant SNP (rs2517959, P = 4.53 × 10−9, OR = 1.13) is located in an intronic region of the gene, ERBB2, which encodes a receptor tyrosine kinase. Several other genes also lie nearby (Figure 1).
The top SNP in the second novel locus, rs12553324, lies within an intergenic region on chromosome 9p21.3 (P = 5.87 × 10−9, OR = 1.12). One SNP in moderate LD (rs10965780; r2 = 0.604 (25)) lies within the promoter flanking region of ELAVL2, which encodes a neuron-specific RNA binding protein (Refseq, November 2015).
The most significant association signal in this study falls within the MAD1L1 gene on chromosome 7p22.3, and has been reported by previous studies of BD or BD plus schizophrenia (SCZ) (8, 26). The top SNP, rs4236274, is located on an intronic region of MAD1L1 (P = 8.49 × 10−12, OR = 0.87). An additional 60 variants at this locus surpassed the genome-wide significance threshold.
The second most significant finding of this study is near the gene TRANK1 on chromosome 3p22.2. This has been identified as a genome-wide significant risk locus for BD by two previous GWAS with partially overlapping samples (7, 9). The same SNP and allele of rs9834970 from those two studies was also significantly associated with BD in the present study (P = 4.83 × 10−10, OR = 0.88).
Twelve variants on chromosome 6q16.1 and ten variants on 12q13.1 also met the genome-wide significance threshold. The top SNP within the 6q16.1 locus (rs1487441, P = 2.58 × 10−8, OR = 1.12) is located in an intergenic region between MIR2113 and POU3F2. Within the 12q13.1 locus, the top SNP (rs1054442, P = 1.20 × 10−8, OR = 1.13) is located within the 3'-UTR of DDN, which encodes dendrin, a cytoskeletal protein expressed at the synapse (27).
We also note nominally significant (p<0.01) support for most of the loci identified in previous GWAS of BD, including markers on chromosome 3p21, and near the genes ADCY2, ANK3, CACNA1C, LMAN2L, NCAN, TENM4, and SYNE1 (Table S2).
Several of the identified loci contain multiple SNPs in tight LD. To determine whether each locus represents a single association signal, we conducted an approximate conditional analysis using GCTA (see methods). The results demonstrated that each of the six GWAS-significant loci (Table 2) was consistent with only one distinct signal (Table S3).
In the X-chromosome analysis, a total of 218,707 markers passed stringent quality control. We did not identify any genome-wide significant signals on the X chromosome (Figure 1).
We also assessed the relative distribution of genomic heritability in the Stage 1 analysis. There was a strong linear relationship between the genomic heritability attributable to each chromosome and chromosome length (P = 0.0004, R2 = 0.45) (Figure S4), consistent with a highly polygenic architecture. Unlike autosomal SNPs, X-linked SNPs explained an unexpectedly small proportion of the heritability (0.2%, Figure S4).
This study is the first GWAS of BD to include samples from the ConLiGen study and to our knowledge the largest published to date. The full set of summary results is available for download at http://www.nimh.nih.gov/labs-at-nimh/research-areas/clinics-and-labs/hgb/data-downloads.shtml. The analysis identified two novel and four known BD risk loci. The results also provided nominally significant support for most loci identified in previous GWAS of BD. No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability.
This study has several limitations. The total sample size is still too small to identify risk variants with small effect sizes or low frequency, especially any residing on the X chromosome. Larger scale studies, such as those ongoing within the Psychiatric Genomics Consortium, will be needed to identify such loci. It has been shown that meaningful increases in statistical power for case-control studies can be obtained by increasing the control-to-case ratio into the range of 4 to 5 (14, 15). Thus we used an excess of controls, including unscreened controls from WTCCC2 and dbGaP. Such unscreened controls are generally easy to obtain and inexpensive, but the actual gain in power may be less than the sample size alone suggests, since some might qualify as cases if examined. However, the population prevalence of BD is probably less than 2% (1, 2), so the impact of undetected cases on power should be small (28). Another limitation arises from the fact that cases enrolled by different studies were ascertained differently, assessed with different diagnostic tools, and fulfilled different, albeit similar, diagnostic criteria. In any case, heterogeneity of ascertainment and clinical diagnosis would tend to reduce power, not lead to false positives (29, 30). Most of BD patients analyzed in this study have been included in previous GWAS studies of BD. Thus, the nominally significant support we observed for many loci identified in previous GWAS of BD cannot be considered as independent evidence of replication. The purpose of this study was not to replicate previous findings but to identify additional risk loci for BD. The sample included more than 2000 BD patients and twenty thousand controls that have not been included in previous BD GWAS.
This study identified two novel loci associated with BD at genome-wide significance. The top SNP within the novel BD risk locus on chromosome 17q12 lies within an intronic region of the gene ERBB2 (Erb-B2 receptor tyrosine kinase 2). Data available through the GTEx Portal (http://www.gtexportal.org/) (31) suggests that this SNP acts as an expression quantitative trait locus (eQTL) for ERBB2 in neural tissue (P = 2.6 × 10−8), but other eQTLs are also present at this locus. ERBB2 is expressed in the brain and encodes a member of the epidermal growth factor (EGF) family of receptor tyrosine kinases, which can form homo-or hetero-dimers with other ERBB proteins. Interestingly, the ERBB proteins act as cell surface receptors for neuregulins (32). This pathway has long been thought to contribute to the pathogenesis of both BD and SCZ (33-37). Two previous gene expression studies have implicated ERBB2 in BD (38, 39), but to our knowledge the present study is the first to demonstrate genetic association with BD. If confirmed in future studies, this locus might be a promising target for novel therapeutics.
The novel risk locus identified on chromosome 9p21.3 is within an intergenic region with no known protein coding genes nearby. A total of 17 highly linked variants in this region (spanning about 17 kb) met the genome-wide significance threshold. Genomic sequence alignments from multiple species suggest that the BD-associated segment is conserved in higher primates. The top SNP is in moderate LD with another SNP that lies within the promoter flanking region of ELAVL2, which encodes a neuron-specific RNA binding protein that promotes neuronal development (40). Different SNPs at this locus have been previously implicated in a GWAS of schizophrenia (41).
Two previous GWAS have reported suggestive evidence of association between BD and common risk variants near MAD1L1 (8, 26). The most significant SNP (rs4332037) reported in the PGC-BD (8) study, which was not genome-wide significant, lies about 54 kb away from, and is in low linkage disequilibrium (CEU r2 = 0.09) with, our top SNP. Ruderfer and colleagues (26) identified MAD1L1 as a genome-wide significant locus in a GWAS that used both BD and SCZ as a combined case definition. No previous study has to our knowledge demonstrated genome-wide significant association between this locus and BD only.
The MooDS-PGC study (9), which overlaps partially with the current study, identified two novel risk loci for BD. One of them is located on 6q16.1, a region between MIR2113 and POU3F2. Our top SNP in this locus (rs1487441) is in perfect LD with rs12202969, the most significant variant in the original MooDS-PGC study. Thus the present study supports the MooDS-PGC finding in a larger sample, but cannot be considered an independent replication.
Another previously reported locus that is supported by the present study is on chromosome 12q13.1. Green et al. (24) reported that an intergenic polymorphism (rs7296288) between RHEBL1 and DHH was significantly associated with BD. In the present study, a SNP (rs105442) in moderate LD (r2 = 0.62) with that reported by Green et al. was also significantly associated with BD. This SNP is located in the 3'-UTR of DDN, encoding dendrin. Dendrin is a synaptic protein that is markedly depleted by sleep deprivation (42), a common trigger of mood episodes in BD. Data available through the GTEx Portal (http://www.gtexportal.org/) (31) suggests that this SNP acts as an eQTL locus for DDN in skeletal muscle tissue (P = 1.1 x 10−19).
In this study, we also carried out an X-chromosome meta-analysis that took advantage of the latest imputation methods and the best available analysis techniques (22, 43). The available sample size was underpowered to detect a common allele that confers a genotype-relative risk (GRR) as low as 1.2. Larger studies are needed to rule out the involvement of common variants within this range of GRR. However, the genomic heritability analyses showed that markers on the X-chromosome contributed very little to the total heritability of BD. While SNP density on this chromosome is lower than on the autosomes, the results suggest that there are few, if any, X-linked markers that play an important role in risk for BD. The association method used in this study is powerful under the assumption of random X-inactivation (43), but may not be optimal when X-inactivation is skewed or incomplete (44). Some candidate-gene association studies (45, 46) have reported association between BD and genes within the pseudoautosomal regions (PARs) of chromosome X. We cannot exclude association with the PAR, since too few markers passed QC for inclusion in the present study.
This meta-analysis study has identified two novel risk loci for BD. The findings support previous work and also suggest novel genetic influences in BD. Increasing sample sizes should enable the identification of additional risk loci for BD, but X-linked markers seem to play little if any role in this common and severe mental illness.
Overall study design
A detailed description of the study design and phenotype assessments for all samples can be found in the Supplementary Materials. This study was carried out in two-stages. Stage 1 comprised a meta-analysis of directly genotyped and imputed SNPs in 7,467 patients diagnosed with bipolar disorder by direct interview and 27,303 controls drawn from published BD case-control studies, dbGaP, and WTCCC2. In Stage 2, a set of 179 variants from Stage 1 with P < 1.0 × 10−6 were tested in an independent sample of 2,313 BD cases and 3,486 controls from two ongoing Swedish GWAS.
Stage 1 samples
Stage 1 comprised cases and controls from 5 published BD GWAS studies (Table 1) and an independent set of 2,072 European-ancestry patients with a long-term diagnosis of BD who were treated with lithium and submitted to the Consortium on Lithium Genetics (ConLiGen) (12). The ConLiGen sample has not been used by any previous GWAS studies of BD. An additional 20,998 genotyped individuals obtained from dbGaP and the WTCCC2 were used as controls. All participants included in the final association tests were of European ancestry.
Stage 2 samples
The Stage 2 sample was predominantly Swedish and exclusively Northern European. BD cases from Sweden were collected through two recruitment streams: 1,908 cases from the Stanley study (47, 48) and 229 cases from the St. Göran Bipolar Project (49). Most control subjects (n=3,113) were randomly selected from Swedish population registers (ascertained on a national basis) and 55 were from the St. Göran Bipolar Project (49). The exclusion criterion for controls was any hospitalization for SCZ or BD. DNA collection procedures have been previously described (50). Both projects were approved by the Regional Ethical Review Board in Stockholm (Sweden), and all participants provided written informed consent. Genotyping was conducted at the Broad Institute of Harvard and MIT using Affymetrix 6.0 (Swedish sample 1) and Illumina OmniExpress (Swedish sample 2) chips.
Quality control
Quality control procedures were carried out separately in each data set. The quality control parameters for retaining SNPs and subjects were: Subject missingness < 0.03; autosomal heterozygosity rate within mean ± 3SD; minor allele frequency (MAF) >= 0.01 (for Affymetrix data, we kept all variants with a MAF >= 0.05); SNP missingness < 0.05; and SNP Hardy-Weinberg equilibrium P > 10−6 in controls (for markers on the X chromosome, only females were used for the Hardy-Weinberg equilibrium tests), no discrepancies between reported sex and sex determined by genotypes on chromosome X. For each data set, around 100K LD-pruned SNPs were used to identify duplicated samples, cryptically related subjects, and population outliers. Relatedness testing was carried out by PLINK. Duplicated samples and cryptically related pairs were identified (Pi_hat > 0.10); only one member of each pair was kept for the data analyses. To identify cryptically related subjects present across different data sets, we tested approximately 20K LD-pruned SNPs present in all of the SNP arrays used by any of the studies. EIGENSOFT (51) was used to identify population outliers (Figure S5). All subjects with apparent non-European ancestry were excluded from the data analyses. After basic QC, we matched data sets by genotyping platform (Table 1).
Genotype imputation was performed using the prephasing/imputation strategy (52) by SHAPEIT2 (53) and IMPUTE2 (54) for both autosomes and the X chromosome. Phase 3 of the 1000 Genomes Project data set (n=2,504) was used as the reference panel for imputation. Appropriate options were used for X chromosome phasing and imputation (–chrX was set for SHAPEIT2 for phasing, and–chrX and gender information were provided to IMPUTE2 for imputation).
Genotype–phenotype association analysis
Gene dosages for all markers with an imputation INFO ≥ 0.5 were used for the final association tests. In total, over 9M genotyped or imputed autosomal SNPs were analyzed. Genotype–phenotype association with imputed allele dosages for autosomal SNPs was carried out with logistic regression as implemented by PLINK (55). The first 10 principal components of population structure were used as covariates in the analyses.
Association tests for markers on the X chromosome were performed with Clayton's "one degree-of-freedom" test, implemented in the snpStats R package (22, 56). An extensive simulation study (43) of several different tests designed specifically for chromosome X association testing concluded that Clayton's "one degree-of-freedom" statistic is robust and powerful across a wide range of realistic conditions.
Meta-analysis of Stage 1 samples
Meta-analysis in Stage 1 was conducted using the sample size-based method in METAL (57). Meta-analysis results were corrected with genomic control to eliminate any residual bias.
Selection of SNPs for Stage 2
All markers with a p-value ≤ 1.0 × 10−6 in Stage 1 (n=179) were selected for validation in the Stage 2 samples, using identical QC and genotype-phenotype association procedures. Of these SNPs, results were available in the Stage 2 samples for 144 SNPs.
Meta-analysis of Stage 1 and Stage 2 samples
Meta-analysis of the Stage 1 and 2 results was conducted using the sample size-based method in METAL, under a fixed effects model. Again, genomic control was used to eliminate any residual bias. Association results were considered genome-wide significant if the meta p-values were < 5 × 10−8and the heterogeneity tests were not significant (p>0.05).
Identification of distinct association signals within risk loci
GCTA (58) was used to identify independently associated variants within each of the 6 GWAS-significant loci. GCTA made use of (i) summary statistics from the meta-analysis of the stage 1 and stage 2 samples, and (ii) genotype data from a reference sample for LD estimation between markers. Study-5 (416 BP cases and 2,741 controls) was used as the reference sample here because subjects from Study-5 were genotyped by the highest density SNP array (Illumina HumanOmni2.5M). GCTA uses a stepwise selection strategy (59) to identify any independent signals through an approximate conditional association analysis.
Genomic heritability estimation of Stage 1 samples
We estimated the genomic heritability (the variance in case-control status explained by all genotyped markers) using a linear mixed model developed by Lee et al. (60). Briefly, a genome relationship matrix (GRM) between all pairs of individuals was estimated from the genome-wide markers. The GRM was then used to estimate variance attributable to markers via residual maximum likelihood (REML) analysis with the first 10 principal components of population structure used as covariates. Results were transformed to the liability scale by assuming a disease prevalence of 2% for BD. For the genomic heritability estimation, we only retained autosomal markers with MAF >0.01 and imputation INFO ≥ 0.9.
We partitioned genomic heritability attributable to each autosome by estimating the GRM from SNPs on each autosome and then fitting the GRMs of all the autosomes simultaneously in the linear mixed model. We further estimated the variance attributable to the X chromosome using a method developed by Yang and colleagues (58) under the assumption of full dosage compensation (complete inactivation of one X chromosome for females).
Power estimation
Power analysis for autosomal markers was done with the Genetic Power Calculator (GPC) (61) under the following assumptions: Trait prevalence 2%, risk allele and marker allele frequency 25%, D-prime 1, genotype-relative risk of 1.15 under a log-additive model. Since excess controls were used in this study and case/control ratio varied across sub-studies, simply using the total sample size might overestimate the power. To take this into account, we used GPC to estimate the non-centrality parameter (NCP) for each study and then iteratively determined the effective symmetric case/control sample size that returns the same NCP (62). The total effective sample sizes of the Stage 1 studies and Stage 1+2 studies were then used for the power estimation. This analysis indicated that the Stage 1 studies had >90% power to detect association at the significance level of p<1 x 10−6, and the combined Stage 1 and 2 studies had >90% power to detect association at the genome-wide significance level of p<5.0 x 10−8.
Power analysis for markers on chromosome X was done with XGWAS (https://github.com/PeteHaitch/XGWAS), which uses a simulation-based method to estimate power. The total effective sample sizes of Stage 1 studies and Stage 1+2 were used for simulations. The simulation results suggested that the stage 1 studies had 65% power to detect a common X-linked allele (MAF ≥ 0.30) that confers a genotype-relative risk of 1.2 at the significance level of p<1 x 10−6, and the combined Stage 1 and 2 studies had 66% power to detect association at the genome-wide significance level of p<5.0 x 10−8.
This work was supported by the National Institute of Mental Health (NIMH) Intramural Research Program (ZIA-MH00284311; NCT00001174) and a NARSAD Young Investigator Award to L.H.
This work utilized the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov)
We obtained several datasets from the database of Genotypes and Phenotypes. A list of investigators and the funding support for these datasets can be found by searching http://www.ncbi.nlm.nih.gov/gap using these accession numbers: phs000124.v2.p1, phs000404.v1.p1, phs000303.v1.p1, phs000203.v1.p1, phs000170.v1.p1, phs000188.v1.p1, and phs000237.v1.p1
This study makes use of data generated by the Wellcome Trust Case-Control Consortium 2 (EGAD00000000021 and EGAD00000000023). We thank the Wellcome Trust Case Control Consortium for making data available for further analysis.
Some data and biomaterials were provided by the Rutgers Cell and DNA Repository.
Some data and biomaterials were collected in four projects that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative. From 1991-98, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN, U01 MH46282, John Nurnberger, M.D., Ph.D., Marvin Miller, M.D., Howard J. Edenberg, Ph.D. and Elizabeth Bowman, M.D.; Washington University, St. Louis, MO, U01 MH46280, Theodore Reich, M.D., Allison Goate, Ph.D., and John Rice, Ph.D.; Johns Hopkins University, Baltimore, MD, U01 MH46274, J. Raymond DePaulo, Jr., M.D., Sylvia Simpson, M.D., MPH, and Colin Stine, Ph.D.; NIMH Intramural Research Program, Clinical Neurogenetics Branch, Bethesda, MD, Elliot Gershon, M.D., Diane Kazuba, B.A., and Elizabeth Maxwell, M.S.W.
NIMH Study 1 – Data and biomaterials were collected as part of ten projects that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative. From 1999-03, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN, R01 MH59545, John Nurnberger, M.D., Ph.D., Marvin J. Miller, M.D., Elizabeth S. Bowman, M.D., N. Leela Rau, M.D., P. Ryan Moe, M.D., Nalini Samavedy, M.D., Rif El-Mallakh, M.D. (at University of Louisville), Husseini Manji, M.D. (at Wayne State University), Debra A. Glitz, M.D. (at Wayne State University), Eric T. Meyer, M.S., Carrie Smiley, R.N., Tatiana Foroud, Ph.D., Leah Flury, M.S., Danielle M. Dick, Ph.D., Howard J. Edenberg, Ph.D.; Washington University, St. Louis, MO, R01 MH059534, John Rice, Ph.D, Theodore Reich, M.D., Allison Goate, Ph.D., Laura Bierut, M.D.; Johns Hopkins University, Baltimore, MD, R01 MH59533, Melvin McInnis, M.D., J. Raymond DePaulo, Jr., M.D., Dean F. MacKinnon, M.D., Francis M. Mondimore, M.D., James B. Potash, M.D., Peter P. Zandi, Ph.D, Dimitrios Avramopoulos, and Jennifer Payne; University of Pennsylvania, PA, R01 MH59553, Wade Berrettini, M.D., Ph.D.; University of California at Irvine, CA, R01 MH60068, William Byerley, M.D., and Mark Vawter, M.D.; University of Iowa, IA, R01 MH059548, William Coryell, M.D., and Raymond Crowe, M.D.; University of Chicago, IL, R01 MH59535, Elliot Gershon, M.D., Judith Badner, Ph.D., Francis McMahon, M.D., Chunyu Liu, Ph.D., Alan Sanders, M.D., Maria Caserta, Steven Dinwiddie, M.D., Tu Nguyen, Donna Harakal; University of California at San Diego, CA, R01 MH59567, John Kelsoe, M.D., Rebecca McKinney, B.A.; Rush University, IL, R01 MH059556, William Scheftner, M.D., Howard M. Kravitz, D.O., M.P.H., Diana Marta, B.S., Annette Vaughn-Brown, M.S.N., R.N., and Laurie Bederow, M.A.; NIMH Intramural Research Program, Bethesda, MD, 1Z01MH002810-01, Francis J. McMahon, M.D., Layla Kassem, PsyD, Sevilla Detera-Wadleigh, Ph.D, Lisa Austin, Ph.D, Dennis L. Murphy, M.D.
NIMH Study 19 – Data and biomaterials were collected for the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a multi-center, longitudinal (5-8 year) project selected from responses to RFP #NIMH-98-DS-0001, "Treatment for Bipolar Disorder." The project was led by Gary Sachs, M.D., and coordinated by Massachusetts General Hospital in Boston, MA. The NIMH grant number was 2N01MH080001-001.
NIMH Study 40 – Data and biomaterials were collected as part of eleven projects (Study 40) that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative. From 2003-2007, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN, R01 MH59545, John Nurnberger, M.D., Ph.D., Marvin J. Miller, M.D., Elizabeth S. Bowman, M.D., N. Leela Rau, M.D., P. Ryan Moe, M.D., Nalini Samavedy, M.D., Rif El-Mallakh, M.D. (at University of Louisville), Husseini Manji, M.D. (at Johnson and Johnson), Debra A. Glitz, M.D. (at Wayne State University), Eric T. Meyer, Ph.D., M.S. (at Oxford University, UK), Carrie Smiley, R.N., Tatiana Foroud, Ph.D., Leah Flury, M.S., Danielle M. Dick, Ph.D (at Virginia Commonwealth University), Howard J. Edenberg, Ph.D.; Washington University, St. Louis, MO, R01 MH059534, John Rice, Ph.D, Theodore Reich, M.D., Allison Goate, Ph.D., Laura Bierut, M.D. K02 DA21237; Johns Hopkins University, Baltimore, M.D., R01 MH59533, Melvin McInnis, M.D., J. Raymond DePaulo, Jr., M.D., Dean F. MacKinnon, M.D., Francis M. Mondimore, M.D., James B. Potash, M.D., Peter P. Zandi, Ph.D, Dimitrios Avramopoulos, and Jennifer Payne; University of Pennsylvania, PA, R01 MH59553, Wade Berrettini, M.D., Ph.D.; University of California at San Francisco, CA, R01 MH60068, William Byerley, M.D., and Sophia Vinogradov, M.D.; University of Iowa, IA, R01 MH059548, William Coryell, M.D., and Raymond Crowe, M.D.; University of Chicago, IL, R01 MH59535, Elliot Gershon, M.D., Judith Badner, Ph.D., Francis McMahon, M.D., Chunyu Liu, Ph.D., Alan Sanders, M.D., Maria Caserta, Steven Dinwiddie, M.D., Tu Nguyen, Donna Harakal; University of California at San Diego, CA, R01 MH59567, John Kelsoe, M.D., Rebecca McKinney, B.A.; Rush University, IL, R01 MH059556, William Scheftner, M.D., Howard M. Kravitz, D.O., M.P.H., Diana Marta, B.S., Annette Vaughn-Brown, M.S.N., R.N., and Laurie Bederow, M.A.; NIMH Intramural Research Program, Bethesda, MD, 1Z01MH002810-01, Francis J. McMahon, M.D., Layla Kassem, Psy.D., Sevilla Detera-Wadleigh, Ph.D, Lisa Austin, Ph.D, Dennis L. Murphy, M.D.; Howard University, William B. Lawson, M.D., Ph.D., Evarista Nwulia, M.D., and Maria Hipolito, M.D. This work was supported by the NIH grants P50CA89392 from the National Cancer Institute and 5K02DA021237 from the National Institute of Drug Abuse.
The Swedish samples were funded by the Stanley Center for Psychiatric Research, Broad Institute from a grant from Stanley Medical Research Institute, the Swedish Research Council (K2014-62X-21445-05-3, K2012-63X-21445-03-2, K2014-62X-14647-12-51 and K2010-61P-21568-01-4), the Söderström-Königska Foundation (SLS-472751), the Swedish foundation for Strategic Research (KF10-0039), and the China Scholarship Council. We would like to thank all of the participants who have kindly given their time and DNA to participate in our research, the Swedish quality register for bipolar disorders (BipoläR), and data collectors at the Department of Medical Epidemiology and Biostatistics (MEB) at Karolinska Institutet for help with recruitment of participants.
The ConLiGen project was in part funded by the Deutsche Forschungsgemeinschaft (DFG; grant no. RI 908/7-1) and the Intramural Research Program of the National Institute of Mental Health (ZIA-MH00284311; NCT00001174). The Romanian sample included in the ConLiGen project was also funded by UEFISCDI, Romania (grant no. 89/2012 awarded to Maria Grigoroiu-Serbanescu, PhD) and BMBF, Germany, grant no. 01GS08144 awarded to M. M. Nöthen and S. Cichon). The Canadian sample has been part of a study funded by the Canadian Institutes of Health Research (grant 64410 to MA). The collection of the Barcelona sample was supported by the Centro de Investigación en Red de Salud Mental (CIBERSAM), IDIBAPS (grant numbers PI080247, PI1200906, PI12/00018) and Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2014SGR1636 and 2014SGR398).
Genotyping was funded in part by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant 01ZX1314G to awarded to Thomas G. Schulze and Marcella Rietschel, grant 01ZX1314A to Sven Cichon and Markus M. Nöthen).
Thomas G. Schulze and Urs Heilbronner received support from the Dr.-Lisa-Oehler-Foundation (Kassel, Germany). Andrea Pfennig, Thomas Stamm, Michael Bauer, Andreas Reif, and Thomas G. Schulze received support from the German Federal Ministry of Education and Research (BMBF) within the framework of the BipolLife network (www.bipolife.org).
M.M.N. is a member of the DFG-funded Excellence-Cluster ImmunoSensation. M.M.N. also received support from the Alfried Krupp von Bohlen und Halbach-Stiftung. The study was supported by the German Research Foundation (DFG; grant ConLiGen RI 908/7-1; grant SFB 636 Z4; grant FOR2107, RI 908/11-1 to M.R., WI 3439/3-1 to S.H.W., NO 246/10-1 to M.M.N.).
The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health. Additional funds were provided by the NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Donors were enrolled at Biospecimen Source Sites funded by NCI\SAIC-Frederick, Inc. (SAIC-F) subcontracts to the National Disease Research Interchange (10XS170), Roswell Park Cancer Institute (10XS171), and Science Care, Inc. (X10S172). The Laboratory, Data Analysis, and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to The Broad Institute, Inc. Biorepository operations were funded through an SAIC-F subcontract to Van Andel Institute (10ST1035). Additional data repository and project management were provided by SAIC-F (HHSN261200800001E). The Brain Bank was supported by a supplements to University of Miami grants DA006227 & DA033684 and to contract N01MH000028. Statistical Methods development grants were made to the University of Geneva (MH090941 & MH101814), the University of Chicago (MH090951, MH090937, MH101820, MH101825), the University of North Carolina - Chapel Hill (MH090936 & MH101819), Harvard University (MH090948), Stanford University (MH101782), Washington University St Louis (MH101810), and the University of Pennsylvania (MH101822). The data used for the analyses described in this manuscript were obtained from the GTEx Portal on 10/12/2015.
The Australian cohort collection was supported by the Australian National Health and Medical Research Council (NHMRC) Program Grants 510135 (PBM) and 1037196 (PBM & PRS); and Project Grants 1063960 (JMF & PRS) and 1066177 (JMF).
The Swiss samples were funded by the Swiss National Science Foundation (grant number 32003B_125469 and NCCR Synapsy, Jean-Michel Aubry aand Alexandre Dayer).
Most importantly, we thank the individuals and families who have participated in and contributed time and data to these studies.
- Bipolar Disorder
- Schizophrenia
- Genome-wide Association Study
- Single Nucleotide Polymorphism
- Minor Allele Frequency
- Odds Ratio
- Standard Deviation
- Confidence Interval
- eQTL
- expression Quantitative Trait Locus
- Genetic Association Information Network – National institute of Mental Health
- Wellcome Trust Case Control Consortium
- Systematic Treatment Enhancement Program for Bipolar Disorder
- Translational Genomics Research Institute
- ConLiGen
- The International Consortium on Lithium Genetics
- BoMA
- Bonn-Mannheim
- dbGaP
- Database of Genotypes and Phenotypes
- Non-Centrality Parameter