Genotype-by-environment interactions inferred from genetic effects on phenotypic variability in the UK Biobank

• Published in: Science advances 2019-08, Vol.5 (8), p.eaaw3538
• Main Authors: Wang, Huanwei, Zhang, Futao, Zeng, Jian, Wu, Yang, Kemper, Kathryn E, Xue, Angli, Zhang, Min, Powell, Joseph E, Goddard, Michael E, Wray, Naomi R, Visscher, Peter M, McRae, Allan F, Yang, Jian
• Format: Article
• Language: English
• Subjects: Biological Specimen Banks; Computer Simulation; Environment; Gene-Environment Interaction; Genetic Predisposition to Disease - genetics; Genetic Variation - genetics; Genome-Wide Association Study; Genotype; Human Genetics; Humans; Obesity - genetics; Quantitative Trait Loci - genetics; Quantitative Trait, Heritable; SciAdv r-articles; White People - genetics
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.aaw3538

Genotype-by-environment interaction (GEI) is a fundamental component in understanding complex trait variation. However, it remains challenging to identify genetic variants with GEI effects in humans largely because of the small effect sizes and the difficulty of monitoring environmental fluctuations. Here, we demonstrate that GEI can be inferred from genetic variants associated with phenotypic variability in a large sample without the need of measuring environmental factors. We performed a genome-wide variance quantitative trait locus (vQTL) analysis of ~5.6 million variants on 348,501 unrelated individuals of European ancestry for 13 quantitative traits in the UK Biobank and identified 75 significant vQTLs with < 2.0 × 10 for 9 traits, especially for those related to obesity. Direct GEI analysis with five environmental factors showed that the vQTLs were strongly enriched with GEI effects. Our results indicate pervasive GEI effects for obesity-related traits and demonstrate the detection of GEI without environmental data.