Behrens, Gundula and Winkler, Thomas W. and Gorski, Mathias and Leitzmann, Michael F. and Heid, Iris M. (2011) To stratify or not to stratify: power considerations for population-based genome-wide association studies of quantitative traits. GENETIC EPIDEMIOLOGY, 35 (8). pp. 867-879. ISSN 0741-0395,
Full text not available from this repository. (Request a copy)Abstract
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. Genet. Epidemiol. 2011. (C) 2011 Wiley Periodicals, Inc.35:867-879, 2011
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENE-ENVIRONMENT INTERACTION; SAMPLE-SIZE REQUIREMENTS; G X E; STATISTICAL POWER; METAANALYSIS; DETECT; TESTS; DISEASE; SNP; genome-wide association; power; stratified analysis; sex-specific; quantitative trait |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 May 2020 09:26 |
| Last Modified: | 26 May 2020 09:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19739 |
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