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

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 obesityrelated 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.