In order to obtain data on the prevalence of genetic factors in a routine care population, a random subgroup of approximately 20-40 percent of the 101,000 screenees will be genotyped for known variants, such as HFE C282Y and H63D, related to iron metabolism and overload. The panel of genotypes to be assayed will reflect the state of knowledge at the time this phase of the study is conducted. In particular, any newly discovered variants related to iron overload and hemochromatosis in non-Caucasian populations, such as for iron overload among Africans, will be included. The results of the genotyping will not directly impact the selection of case and control participants; case/control selection will be based only on the transferrin saturation/serum ferritin screen results. It is likely that many HFE genotype positive persons will have confirmed elevations of transferrin saturation and thus may get selected as confirmed elevated transferrin saturation case participants. Genotype positive persons with non-elevated transferrin saturation levels, who are not randomly selected as controls, will constitute a third group and undergo the same intensive studies as cases and controls. A random sample of the individuals being recruited to participate in the genotyping subgroup will be surveyed to determine their knowledge and attitudes about, interest in, and support for such screening programs. Both qualitative and quantitative measures will be employed. Efforts will be made to ascertain reasons for refusal and related information from those who decline participation. In addition, 2,000 primary care patients will be selected to participate in a substudy comparing phenotype- versus genotype-based screening and testing methods.