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Research Designs for the Study of Gene-Environment Interactions in Psychiatric DisordersReport of a Foundations Fund for Research in Psychiatry Panel
Kenneth K. Kidd, PhD;
Steven Matthysee, PhD
Arch Gen Psychiatry. 1978;35(8):925-932.
Abstract
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Understanding the genetic and environmental contributions (and their interactions, which are likely to be complex) to the etiology of psychiatric disorders requires research designs incorporating many basic principles of genetics. Genetic variation is likely to contribute to psychiatric disorders and genetic heterogeneity is likely to exist for any single disorder, ie, completely different genetic variants may each be capable of increasing an individual's susceptibility to the disorder. Thus, it is important to define phenotypes that may more closely reflect each individual genetic variant rather than to rely solely on the psychiatric diagnosis. Research should be undertaken with the goal of testing specific hypotheses that can be excluded. Research designs can include studies of unrelated individuals, twins, separated relatives, nuclear families, or extended pedigrees. Not all hypotheses can be tested on one type of data, and appropriate analytic methods vary. Because genetic hypotheses cannot be tested on studies of unrelated individuals, it is important that data be collected on families instead of unrelated individual patients and/or controls. Studies should include traits that bridge the gap between the genotype and the diagnostic phenotype. Such studies should be multidisciplinary, and the best statistical-genetics methodology should be used for data analysis.
Author Affiliations
From the Department of Human Genetics, Yale University School of Medicine, New Haven, Conn (Dr Kidd); and the Mailman Research Center, McLean Hospital, Belmont, Mass (Dr Matthysee).
Footnotes
Accepted for publication March 4, 1978.
Reprint requests to Foundations Fund, 100 York St, 2A, New Haven, CT 06510 (Ms Lois Young).
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