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Conditions which arise from single gene defects demonstrate a simple mendelian mode of inheritance. There are however a large number of common conditions in which genetic factors are thought to be involved but are not clearly passed from one individual to another and merely cluster in families. Such observations raise a number of questions including: what is the size of the genetic contribution to the disorder and how might the susceptibility gene(s) involved in the development of the condition be identified ?
The National Academy of Sciences-National Research Council twin registry of almost 16 000 twin pairs reported concordance rates for cirrhosis of 16.9% in monozygotic twins and 5.3% in dizygotic twins, implying a genetic predisposition to this complication of alcohol abuse.1 Although it is possible that twins share not only genes but a similar environment, with greater (in utero) environmental sharing in monozygotic twins, there is increasing epidemiological2 and laboratory3 evidence to support a genetic basis to familial clustering. However, the concordance rate for alcoholic liver disease in monozygotic twins falls well below 100%, highlighting the role of environmental as well as genetic factors.
The magnitude of the genetic contribution to disease is not easy to assess in common disorders. The overall …