Polygenic and socioeconomic risk for high body mass index: 69 years of follow-up across life

Abstract

BackgroundGenetic influences on body mass index (BMI) appear to markedly differ across life, yet existing research is equivocal and limited by a paucity of life course data. Better understanding changes across life in the determinants of BMI may inform etiology, the timing of preventative efforts, and the interpretation of increasing number of studies utilizing genetically-informed designs to study BMI. We thus used a birth cohort study to investigate differences in association and explained variance in the polygenic prediction of BMI from infancy to old age (2-69 years) in a single sample. A secondary aim was to investigate how a key purported environmental influence on BMI (childhood socioeconomic position) differed across life, and whether it operated independently and/or multiplicatively of genetic influences.MethodsData were from up to 2677 participants in the MRC National Survey of Health and Development, with measured weight and height from infancy to old age (12 timepoints from 2-69 years) and genetic data (obtained from blood samples at 53 years). We derived three polygenic indices derived from GWAS of a) adult BMI, b) recalled childhood body size, and c) childhood-adolescence BMI. We investigated associations of each polygenic index and BMI at each age and compared in terms of absolute effect size (β) and explained variance (R2). We used linear and quantile regression models, and finally investigated the additive or multiplicative role of childhood socioeconomic position.ResultsMean BMI and its variance increased across adulthood. For polygenic liability to higher adult BMI (Khera et al), the trajectories of effect size (β) and explained variance (R2) diverged: explained variance peaked in early adulthood and plateaued thereafter, while absolute effect sizes increased throughout adulthood. For polygenic liability to higher childhood BMI, explained variance was largest in adolescence and early adulthood; effect sizes were marginally smaller in absolute terms from adolescence to adulthood. All polygenic indices were related to higher variation in BMI; effect sizes were sizably larger at the upper end of the BMI distribution. Socioeconomic and polygenic risk for higher BMI across life appear to operate additively; we found little evidence of interaction.ConclusionOur findings highlight the likely independent influences of polygenic and socioeconomic factors on BMI across life. Despite sizable associations, the BMI variance explained by each plateaued or declined across adulthood while BMI variance itself increased. This is suggestive of the increasing importance of chance (‘non-shared’) environmental influences on BMI across life.