Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (snp) may reflect underlying gene-environment (g×e) or gene-gene interactions. we modeled variance heterogeneity for blood lipids and bmi in up to 44,211 participants and investigated relationships between variance effects (pv),g×e interaction effects (with smoking and physical activity),and marginal genetic effects (pm). correlations between pvand pmwere stronger for snps with established marginal effects (spearman’s ρ = 0.401 for triglycerides,and ρ = 0.236 for bmi) compared to all snps. when pvand pmwere compared for all pruned snps,only bmi was statistically significant (spearman’s ρ = 0.010). overall,snps with established marginal effects were overrepresented in the nominally significant part of the pvdistribution (pbinomial<0.05). snps from the top 1% of the pmdistribution for bmi had more significant pvvalues (pmann–whitney= 1.46×10−5),and the odds ratio of snps with nominally significant (<0.05) pmand pvwas 1.33 (95% ci: 1.12,1.57) for bmi. moreover,bmi snps with nominally significant g×e interaction p-values (pint<0.05) were enriched with nominally significant pvvalues (pbinomial= 8.63×10−9and 8.52×10−7for snp × smoking and snp × physical activity,respectively). we conclude that some loci with strong marginal effects may be good candidates for g×e,and variance-based prioritization can be used to identify them. © 2017 shungin et al.