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- Title
Polygenic and socioeconomic risk for high body mass index: 69 years of follow-up across life.
- Authors
Bann, David; Wright, Liam; Hardy, Rebecca; Williams, Dylan M.; Davies, Neil M.
- Abstract
Genetic 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. We thus used a birth cohort study to investigate differences in association and explained variance in polygenic risk for high BMI across infancy to old age (2–69 years). A secondary aim was to investigate how the association between BMI and a key purported environmental determinant (childhood socioeconomic position) differed across life, and whether this operated independently and/or multiplicatively of genetic influences. Data were from up to 2677 participants in the MRC National Survey of Health and Development, with measured BMI at 12 timepoints from 2–69 years. We used multiple polygenic indices from GWAS of adult and childhood BMI, and investigated their associations with BMI at each age. For polygenic liability to higher adult BMI, 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; quantile regression analyses showed that 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. Our 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. Author summary: We sought to better understand how polygenic and socioeconomic risk for high body mass index (BMI) differed across life, using data from a birth cohort followed-up from 2 to 69 years. High polygenic risk for adult BMI was associated with greater absolute differences in BMI at older ages, yet the explained variance peaked in early adulthood and plateaued thereafter. For polygenic risk for high childhood BMI, explained variance was largest in adolescence and early adulthood; effect sizes were marginally smaller from adolescence to adulthood. Low socioeconomic position was also associated with high BMI—effect sizes increased across life yet explained variance plateaued across adulthood. The discrepancy between effect sizes and explained variance was likely due to the phenotypic variance in BMI increasing across life: the increase in BMI variance matched or exceeded the increase in effect sizes. Inasmuch as our study captured key genetic and shared environmental influences on BMI, our findings suggest that chance ('non-shared') environmental influences may be increasingly important for BMI at later ages. Finally, we found little evidence for interactions between socioeconomic position and polygenic indices; rather, both were independently associated with BMI. Our findings thus highlight the importance of both environmental and genetic factors for BMI across life.
- Subjects
MONOGENIC &; polygenic inheritance (Genetics); BODY mass index; QUANTILE regression; COHORT analysis; ADULTS
- Publication
PLoS Genetics, 2022, Vol 18, Issue 7, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1010233