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- Title
Gene-environment interaction explains a part of missing heritability in human body mass index.
- Authors
Jung, Hae-Un; Kim, Dong Jun; Baek, Eun Ju; Chung, Ju Yeon; Ha, Tae Woong; Kim, Han-Kyul.; Kang, Ji-One; Lim, Ji Eun; Oh, Bermseok
- Abstract
Gene-environment (G×E) interaction could partially explain missing heritability in traits; however, the magnitudes of G×E interaction effects remain unclear. Here, we estimate the heritability of G×E interaction for body mass index (BMI) by subjecting genome-wide interaction study data of 331,282 participants in the UK Biobank to linkage disequilibrium score regression (LDSC) and linkage disequilibrium adjusted kinships–software for estimating SNP heritability from summary statistics (LDAK-SumHer) analyses. Among 14 obesity-related lifestyle factors, MET score, pack years of smoking, and alcohol intake frequency significantly interact with genetic factors in both analyses, accounting for the partial variance of BMI. The G×E interaction heritability (%) and standard error of these factors by LDSC and LDAK-SumHer are as follows: MET score, 0.45% (0.12) and 0.65% (0.24); pack years of smoking, 0.52% (0.13) and 0.93% (0.26); and alcohol intake frequency, 0.32% (0.10) and 0.80% (0.17), respectively. Moreover, these three factors are partially validated for their interactions with genetic factors in other obesity-related traits, including waist circumference, hip circumference, waist-to-hip ratio adjusted with BMI, and body fat percentage. Our results suggest that G×E interaction may partly explain the missing heritability in BMI, and two G×E interaction loci identified could help in understanding the genetic architecture of obesity. A study on the effects of gene-environment interactions on body mass index (BMI) in the UK Biobank cohort finds BMI genetic loci that interact with lifestyle traits such as physical activity, smoking, and alcohol consumption.
- Subjects
UNITED Kingdom; HERITABILITY; GENOTYPE-environment interaction; BODY mass index; HUMAN body; WAIST-hip ratio; LINKAGE disequilibrium
- Publication
Communications Biology, 2023, Vol 6, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-023-04679-4