Gene-environment interaction explains a part of missing heritability in human body mass index

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. Gene-environment (GxE) interaction could partially explain missing heritability in traits; however, the magnitudes of GxE interaction effects remain unclear. Here, we estimate the heritability of GxE 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 GxE 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 GxE interaction may partly explain the missing heritability in BMI, and two GxE interaction loci identified could help in understanding the genetic architecture of obesity.

Automated summary

A study on gene-environment interactions on BMI in the UK Biobank cohort finds that BMI genetic loci interact with lifestyle traits such as physical activity, smoking, and alcohol consumption. GxE interaction could partially explain missing heritability in traits, but the magnitudes of GxE interaction effects remain unclear.