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Behrens, G.* ; Winkler, T.W.* ; Gorski, M. ; Leitzmann, M.F.* ; Heid, I.M.

To stratify or not to stratify: Power considerations for population-based genome-wide association studies of quantitative traits.

Genet. Epidemiol. 35, 867-879 (2012)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Meta-analyses of genome-wide association studies require numerous study partners to conduct pre-defined analyses and thus simple but efficient analyses plans. Potential differences between strata (e.g. men and women) are usually ignored, but often the question arises whether stratified analyses help to unravel the genetics of a phenotype or if they unnecessarily increase the burden of analyses. To decide whether to stratify or not to stratify, we compare general analytical power computations for the overall analysis with those of stratified analyses considering quantitative trait analyses and two strata. We also relate the stratification problem to interaction modeling and exemplify theoretical considerations on obesity and renal function genetics. We demonstrate that the overall analyses have better power compared to stratified analyses as long as the signals are pronounced in both strata with consistent effect direction. Stratified analyses are advantageous in the case of signals with zero (or very small) effect in one stratum and for signals with opposite effect direction in the two strata. Applying the joint test for a main SNP effect and SNP-stratum interaction beats both overall and stratified analyses regarding power, but involves more complex models. In summary, we recommend to employ stratified analyses or the joint test to better understand the potential of strata-specific signals with opposite effect direction. Only after systematic genome-wide searches for opposite effect direction loci have been conducted, we will know if such signals exist and to what extent stratified analyses can depict loci that otherwise are missed.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter genome-wide association; power; stratified analysis; sex-specific; quantitative trait
ISSN (print) / ISBN 0741-0395
e-ISSN 1098-2272
Zeitschrift Genetic Epidemiology
Quellenangaben Band: 35, Heft: 8, Seiten: 867-879 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort New York, N.Y.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Genetic Epidemiology (IGE)