ArticleCommunications biology2023
Gene-environment interaction explains a part of missing heritability in human body mass index.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Design and model choices shape inference of age-varying genetic effects on complex traits.Nature aging · 2026Article
- UK Biobank whole-genome sequencing reveals robust contributions of rare variants to complex-trait heritability.Genome biology · 2026Article
- Genetics of Thyroid Function: Relevance for Biology and Disease Management.The Journal of clinical endocrinology and metabolism · 2025Review
- Steatotic liver disease interacts with a polygenic risk score for triglyceride clearance to impact the risk of hypertriglyceridaemia: The Maastricht Study.Diabetologia · 2025Article
- Improvement of polygenic modeling of blood pressure traits using lifestyle information in the UK Biobank.Genetics · 2025Article
- Gene-by-environment Interactions and Adaptive Body Size Variation in Mice From the Americas.Molecular biology and evolution · 2025Article
- Multi-omics approaches for understanding gene-environment interactions in noncommunicable diseases: techniques, translation, and equity issues.Human genomics · 2025Review
- Article
- Variant level heritability estimates of type 2 diabetes in African Americans.Scientific reports · 2024Article
- Generalizability of polygenic prediction models: how is the RBMC medical genomics · 2024Article
- A versatile, fast and unbiased method for estimation of gene-by-environment interaction effects on biobank-scale datasets.Nature communications · 2023Article
- Gene-environment interactions and the effect on obesity risk in low and middle-income countries: a scoping review.Frontiers in endocrinology · 2023Article
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Authors and funding
9 authors.
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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.
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