Abstract
Book Foreword: A major challenge confronting researchers is to understand how environmental risk factors generate the symptoms of a disordered mind or body. Early findings that identified single-gene causes of rare Mendelian conditions have proven difficult to extend more generally. The alternative gene-environment interaction approach assumes that environmental pathogens cause disorder, whereas genes influence susceptibility to environmental pathogens. This approach is based on two key observations: multifactorial disorders have known environmental causes; and people show heterogeneity in their response to those causes (i.e. not all people exposed succumb). Understanding who succumbs under what conditions will make personalized health-care a reality. There are a number of methodological concerns that continue to plague genetic epidemiological research. This book analyzes the ways in which genetic epidemiologists can meet the challenges posed by concerns about: (1) the need for very large sample sizes in genetics research; (2) confounding by ethnic stratification; (3) confounding by gene-environment correlation; (4) difficulties of achieving precise and reliable measures of environmental exposure, particularly if exposure typically occurs over long times; (5) concerns about low prior probabilities of a true association between a disorder and any one of thousands of genetic polymorphisms; and (6) questions about how best to integrate experimental science with epidemiology. This is desirable because traditional genetic epidemiology cannot tell us much about the biological mechanisms involved in an interaction.