Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, South Korea.
Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South Korea.
Commun Biol. 2023 Mar 25;6(1):324. doi: 10.1038/s42003-023-04679-4.
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.
基因-环境（G×E）相互作用可以部分解释性状中缺失的遗传率；然而，G×E 相互作用的效应大小仍不清楚。在这里，我们通过对英国生物库中 331282 名参与者的全基因组相互作用研究数据进行连锁不平衡评分回归（LDSC）和连锁不平衡调整的基于关系软件（LDAK-SumHer）分析，来估计体重指数（BMI）的 G×E 相互作用的遗传率。在 14 个与肥胖相关的生活方式因素中，MET 评分、吸烟包年数和饮酒频率在这两种分析中均与遗传因素显著相互作用，占 BMI 的部分方差。LDSC 和 LDAK-SumHer 分析这些因素的 G×E 相互作用遗传率（%）及其标准误如下：MET 评分分别为 0.45%（0.12）和 0.65%（0.24）；吸烟包年数分别为 0.52%（0.13）和 0.93%（0.26）；饮酒频率分别为 0.32%（0.10）和 0.80%（0.17）。此外，这三个因素在其他与肥胖相关的特征（包括腰围、臀围、BMI 校正的腰臀比和体脂百分比）中与遗传因素的相互作用得到了部分验证。我们的研究结果表明，G×E 相互作用可能部分解释了 BMI 中缺失的遗传率，并且确定的两个 G×E 相互作用位点有助于理解肥胖的遗传结构。
