| Title: | A fast and powerful linear mixed model approach for genotype-environment interaction tests in large-scale GWAS |
| Journal: | Briefings in Bioinformatics |
| Published: | 21 Dec 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36545787/ |
| DOI: | https://doi.org/10.1093/bib/bbac547 |
| URL: | https://academic.oup.com/bib/article-pdf/24/1/bbac547/48782647/bbac547.pdf |
| Citations: | 7 (7 in last 2 years) as of 8 Aug 2024 |
Publication 10839
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Abstract
Genotype-by-environment interaction (GEI or GxE) plays an important role in understanding complex human traits. However, it is usually challenging to detect GEI signals efficiently and accurately while adjusting for population stratification and sample relatedness in large-scale genome-wide association studies (GWAS). Here we propose a fast and powerful linear mixed model-based approach, fastGWA-GE, to test for GEI effect and G + GxE joint effect. Our extensive simulations show that fastGWA-GE outperforms other existing GEI test methods by controlling genomic inflation better, providing larger power and running hundreds to thousands of times faster. We performed a fastGWA-GE analysis of ~7.27 million variants on 452 249 individuals of European ancestry for 13 quantitative traits and five environment variables in the UK Biobank GWAS data and identified 96 significant signals (72 variants across 57 loci) with GEI test P-values < 1 × 10-9, including 27 novel GEI associations, which highlights the effectiveness of fastGWA-GE in GEI signal discovery in large-scale GWAS.</p>
5 Authors
- Wujuan Zhong
- Aparna Chhibber
- Lan Luo
- Devan V Mehrotra
- Judong Shen
1 Application
| Application ID | Title |
|---|---|
| 28967 | Predicting drug efficacy, potential adverse outcomes, and causal biology through phenome-wide association studies (PheWAS) and Mendelian randomization |
Enabling scientific discoveries that improve human health