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A meta-analysis approach with filtering for identifying gene-level gene-environment interactions.
- Source :
-
Genetic epidemiology [Genet Epidemiol] 2018 Jul; Vol. 42 (5), pp. 434-446. Date of Electronic Publication: 2018 Feb 11. - Publication Year :
- 2018
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Abstract
- There is a growing recognition that gene-environment interaction (G × E) plays a pivotal role in the development and progression of complex diseases. Despite a wealth of genetic data on various complex diseases/traits generated from association and sequencing studies, detecting G × E via genome-wide analysis remains challenging due to power issues. In genome-wide G × E studies, a common strategy to improve power is to first conduct a filtering test and retain only the genetic variants that pass the filtering step for subsequent G × E analyses. Two-stage, multistage, and unified tests have been proposed to jointly consider the filtering statistics in G × E tests. However, such G × E tests based on data from a single study may still be underpowered. Meanwhile, large-scale consortia have been formed to borrow strength across studies and populations. In this work, motivated by existing single-study G × E tests with filtering and the needs for meta-analysis G × E approaches based on consortia data, we propose a meta-analysis framework for detecting gene-based G × E effects, and introduce meta-analysis-based filtering statistics in the gene-level G × E tests. Simulations demonstrate the advantages of the proposed method-the ofGEM test. We apply the proposed tests to existing data from two breast cancer consortia to identify the genes harboring genetic variants with age-dependent penetrance (i.e., gene-age interaction effects). We develop an R software package ofGEM for the proposed meta-analysis tests.<br /> (© 2018 WILEY PERIODICALS, INC.)
Details
- Language :
- English
- ISSN :
- 1098-2272
- Volume :
- 42
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Genetic epidemiology
- Publication Type :
- Academic Journal
- Accession number :
- 29430690
- Full Text :
- https://doi.org/10.1002/gepi.22115