Winkler, Thomas W. and Justice, Anne E. and Cupples, L. Adrienne and Kronenberg, Florian and Kutalik, Zoltan and Heid, Iris M. (2017) Approaches to detect genetic effects that differ between two strata in genome-wide meta-analyses: Recommendations based on a systematic evaluation. PLOS ONE, 12 (7): e0181038. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Genome-wide association meta-analyses (GWAMAs) conducted separately by two strata have identified differences in genetic effects between strata, such as sex-differences for body fat distribution. However, there are several approaches to identify such differences and an uncertainty which approach to use. Assuming the availability of stratified GWAMA results, we compare various approaches to identify between-strata differences in genetic effects. We evaluate type I error and power via simulations and analytical comparisons for different scenarios of strata designs and for different types of between-strata differences. For strata of equal size, we find that the genome-wide test for difference without any filtering is the best approach to detect stratum-specific genetic effects with opposite directions, while filtering for overall association followed by the difference test is best to identify effects that are predominant in one stratum. When there is no a priori hypothesis on the type of difference, a combination of both approaches can be recommended. Some approaches violate type I error control when conducted in the same data set. For strata of unequal size, the best approach depends on whether the genetic effect is predominant in the larger or in the smaller stratum. Based on real data from GIANT (>175 000 individuals), we exemplify the impact of the approaches on the detection of sex-differences for body fat distribution (identifying up to 10 loci). Our recommendations provide tangible guidelines for future GWAMAs that aim at identifying between-strata differences. A better understanding of such effects will help pinpoint the underlying mechanisms.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BODY-MASS INDEX; ENVIRONMENT INTERACTION; QUANTITATIVE TRAITS; FAT DISTRIBUTION; ASSOCIATION; LOCI; SUSCEPTIBILITY; EPIDEMIOLOGY; EFFICIENT; VARIANTS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:16 |
| Last Modified: | 27 Feb 2019 14:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1521 |
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