Imputing gene-treatment interactions when the genotype distribution is unknown using case-only and putative placebo analyses--a new method for the Genetics of Hypertension Associated Treatment (GenHAT) study.

TitleImputing gene-treatment interactions when the genotype distribution is unknown using case-only and putative placebo analyses--a new method for the Genetics of Hypertension Associated Treatment (GenHAT) study.
Publication TypeJournal Article
Year of Publication2004
AuthorsDavis, BR, Ford, CE, Boerwinkle, E, Arnett, D, Eckfeldt, J, Black, H
JournalStat Med
Volume23
Issue15
Pagination2413-27
Date Published2004 Aug 15
ISSN0277-6715
KeywordsControlled Clinical Trials as Topic, Genotype, Humans, Hypertension, Placebos, United States
Abstract

There is a sizeable literature on methods for detecting gene-environment interaction in the framework of case-control studies, particularly with reference to the assumption of independence of genotype and exposure. In the context of a clinical trial, wherein gene-drug interactions with regard to outcomes are examined, these methods may be readily applied, as gene and drug are independent by randomization. In an active-controlled trial (experimental treatment vs standard) that has collected genotype information, gene-drug interactions can be estimated. In addition, the effect of the experimental treatment vs placebo can be imputed by using data from a historical placebo-controlled trial (standard vs placebo) if either (a) genotype information is available from the historical trial or (b) assumptions are made about the prevalence of genotype and the odds ratios of genotype and disease in the historical trial using information from other studies. Motivation for these procedures is provided by the Genetics of Hypertension Associated Treatment, a large pharmacogenetics, ancillary study of a hypertension clinical trial, and examples from published hypertension trials will be used to illustrate the methods.

DOI10.1002/sim.1831
Alternate JournalStat Med
PubMed ID15273956
Grant ListR01 HL083498 / HL / NHLBI NIH HHS / United States
R01-HL60382 / HL / NHLBI NIH HHS / United States

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