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Genetic factors for alcohol dependence and schizophrenia: common and rare variants.

Alcohol dependence (AD) is a complex disease, with devastating effects on individuals, families and society. It is estimated that 76.3 million people worldwide suffered from alcohol use disorders (AUD) (WHO, 2004). In the United States (US), more than18 million adults (7% of the population) have been diagnosed with AUD including alcohol abuse or dependence (Li et al., 2004). Family, twin, and adoption studies have indicated that genetic and environmental factors and their interactions contribute to the development of AD, with a heritability of more than 0.5 (Goldman et al., 2005; Heath et al., 1997; Schuckit, 2000). 
 
Schizophrenia (SCZ) is a mental disorder characterized by auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking with significant social or occupational dysfunction. It is estimated that 1% of the population may suffer from schizophrenia worldwide (Mowry 2001). Approximately 2.4 million US adults (about 1.1 percent of the population aged 18 and older in a given year) have schizophrenia (Regier 1993, US census bureau 2005). SCZ is a multifactorial disorder characterized, to a large extent, by the contribution of multiple susceptibility genes, which may interact, in a stochastic manner, with epigenetic processes and environmental factors (Karayiorgou et al., 2006; Danese, 2006). SCZ is known to be a multifactorial disorder with a demonstrated heritability of 80% in family studies and meta-analysis of multiple twin studies (Gejman et al., 2010; Sullivan 2003). 
 
Epidemiological studies have shown that there is a high alcohol/substance use disorder comorbidity rate in schizophrenia; however, the interrelationship between AD and SCZ is very complex. Previous study has suggested that chronic alcohol dependence alone can result in a chronic, schizophrenia-like psychosis (alcoholic hallucinosis) which cannot be distinguished from schizophrenia on the basis of psychopathological or clinical symptoms; however, recent clinical and epidemiological studies have pointed at a significantly increased prevalence for substance abuse and dependence in schizophrenia, especially of alcohol (Soyka 1994). However, the hypothesis that substance abuse causes schizophrenia is not generally supported (Hambrecht 96). Recently, one study has reported that individuals with SCZ are at increased risk for developing substance abuse disorders (Krystal et al., 2006); while another study has indicated that approximately every fifth patient with schizophrenia has lifetime AUD diagnosis (Koskinen 2009). More recently, it is suggested that AUDs are a common sequela of schizophrenia (Jones 2011).