Gene-environment interactions contribute to blood pressure variation across global populations

Understanding the interplay between genetics and environment is essential for elucidating the biological basis of complex traits such as blood pressure (BP). Although gene-environment interactions (G×E) contribute to BP variation, their role in multi-ancestry cohorts remains underexplored. We hypothesize that G×E may explain additional variance in BP across diverse populations, where environmental exposures and genetic backgrounds are more heterogeneous. Here, we evaluate the importance of G×E on diastolic pressure (DP), systolic pressure (SP), and pulse pressure (PP) in a multi-ethnic subset of 24,000 UK Biobank individuals. We considered 23 lifestyle variables as the environmental exposures and estimated variance components attributed to genetic effects, environmental effects, and gene-environment interactions. Our results revealed that G×E accounts for 7% of variance in DP, 4% in SP, and 3% in PP. While these estimates are not statistically different from the ones obtained from an analysis restricted to White British individuals using the same lifestyle variables and methodology (4%, 3%, and 4% for DP, SP, and PP, respectively), the point estimate for DP is almost twice as large in the multi-ethnic sample. Including G×E in the models did not improve out-of-sample prediction accuracy. We also performed a G×E genome-wide association study (G×E-GWAS) to uncover individual interactions affecting BP traits. Although no interaction surpassed genome-wide significance, suggestive hits were enriched in BP-relevant pathways. Our hypothesis-generating study suggests that higher environmental and genetic heterogeneity in multi-ethnic cohorts may amplify the role of G×E for some traits and serves as a basis for future studies with larger sample sizes and higher power.