The Genom of Homo sapiens.pdf

360 MERIKANGASidentification of genes. This is primarily attributable to theindirect nature of the evidence that environmental factorsplay a key etiologic role.On the basis of family and twin studies, it is possible toidentify the relative contribution of genetic and environmentalfactors. Evidence for environmental influences includes:discordant monozygotic twins; greater than a 50%diminution in risk in relatives than expected by degree ofgenetic relatedness; and greater concordance for monozygotictwins reared together compared to those reared apart.For example, our recent review of a series of complex diseasesrevealed that multiple sclerosis, type I diabetes,autism, and schizophrenia are more strongly influenced bygenetic risk factors; breast cancer, type II diabetes, andAlzheimer’s disease are vulnerable to both genetic and environmentalsusceptibility; and environmental exposuresare necessary for the development of alcohol and drugabuse, cervical cancer, and AIDS, but genes may determinethe extent to which exposure is associated with disease,infection, or cancer (Merikangas and Risch 2003).CONTRIBUTION OF EPIDEMIOLOGYTO THE FUTURE OF GENETICSThe importance of epidemiology to the future of geneticshas been described by numerous geneticists and epidemiologistswho conclude that the best strategy for geneidentification will ultimately involve large epidemiologicstudies in diverse populations (Risch and Merikangas1996; Khoury and Yang 1998; Risch 2000; Thomas2000; Yang et al. 2000; Merikangas 2002; Merikangas etal. 2002; Khoury et al. 2003). It is likely that populationbasedassociation studies will assume increasing importancein translating the products of genomics to publichealth (Risch and Merikangas 1996). The term “humangenome epidemiology” was coined by Khoury (Khouryet al. 2003) to denote the emerging field that employs systematicapplications of epidemiologic methods in population-basedstudies to study the impact of human geneticvariation on health and disease.Genetic EpidemiologyApplying the tools of genetic epidemiology, particularlywhen coupled with continued progress in basicbiomedical sciences, is likely to be one of the most fruitfulapproaches to resolving etiologic factors underlyingdisorders and translating the progress being made in genomicsto the public (Merikangas 2002). Figure 1 showsthe classic epidemiologic triangle that illustrates the majorfocus of epidemiologic investigations: the products ofthe interaction between the host, an infectious or othertype of agent, and the environment that promotes the exposure(Gordis 2000). The field of genetic epidemiologyfocuses on the role of genetic factors that interact withother domains of risk to enhance vulnerability or protectionagainst disease (King et al. 1984; Khoury et al. 1993;Ellsworth and Manolio 1999a,b). It is quite conceivablethat several combinations of these risk factors could producesimilar phenotypes in susceptible individuals. Thetest for epidemiology over the next decades will be theextent to which its tools can be refined to capture thesesituations. The key aspects of the epidemiologic methodthat discriminate it from traditional genetic study designsare described below.Study designs. Epidemiologic studies generally proceedfrom retrospective case-control studies designed todevelop specific hypotheses to prospective cohort studiesthat can test causal associations. The major goal of ana-Figure 1. The epidemiologic triangle.