The heritable basis of gene–environment interactions in cardiometabolic traits

AIMS/HYPOTHESIS: Little is known about the heritable basis of gene–environment interactions in humans. We therefore screened multiple cardiometabolic traits to assess the probability that they are influenced by genotype–environment interactions. METHODS: Fourteen established environmental risk exposures and 11 cardiometabolic traits were analysed in the VIKING study, a cohort of 16,430 Swedish adults from 1682 extended pedigrees with available detailed genealogical, phenotypic and demographic information, using a maximum likelihood variance decomposition method in Sequential Oligogenic Linkage Analysis Routines software. RESULTS: All cardiometabolic traits had statistically significant heritability estimates, with narrow-sense heritabilities (h (2)) ranging from 24% to 47%. Genotype–environment interactions were detected for age and sex (for the majority of traits), physical activity (for triacylglycerols, 2 h glucose and diastolic BP), smoking (for weight), alcohol intake (for weight, BMI and 2 h glucose) and diet pattern (for weight, BMI, glycaemic traits and systolic BP). Genotype–age interactions for weight and systolic BP, genotype–sex interactions for BMI and triacylglycerols and genotype–alcohol intake interactions for weight remained significant after multiple test correction. CONCLUSIONS/INTERPRETATION: Age, sex and alcohol intake are likely to be major modifiers of genetic effects for a range of cardiometabolic traits. This information may prove valuable for studies that seek to identify specific loci that modify the effects of lifestyle in cardiometabolic disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-016-4184-0) contains peer-reviewed but unedited supplementary material, which is available to authorised users.