A meta-analysis approach with filtering for identifying gene-level gene-environment interactions.
Genet Epidemiol
; 42(5): 434-446, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-29430690
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interação Gene-Ambiente
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article