Abstract
African ancestry individuals with comparable overall anthropometric measures to Europeans have lower abdominal adiposity. To explore the genetic underpinning of different adiposity patterns, we investigated whether genetic risk scores for well-studied adiposity phenotypes like body mass index (BMI) and waist circumference (WC) also predict other, less commonly measured adiposity measures in 2420 African American individuals from the Jackson Heart Study. Polygenic risk scores (PRS) were calculated using GWAS-significant variants extracted from published studies mostly representing European ancestry populations for BMI, waist-hip ratio (WHR) adjusted for BMI (WHRBMIadj), waist circumference adjusted for BMI (WCBMIadj), and body fat percentage (BF%). Associations between each PRS and adiposity measures including BF%, subcutaneous adiposity tissue (SAT), visceral adiposity tissue (VAT) and VAT:SAT ratio (VSR) were examined using multivariable linear regression, with or without BMI adjustment. In non-BMI adjusted models, all phenotype-PRS were found to be positive predictors of BF%, SAT and VAT. WHR-PRS was a positive predictor of VSR, but BF% and BMI-PRS were negative predictors of VSR. After adjusting for BMI, WHR-PRS remained a positive predictor of BF%, VAT and VSR but not SAT. WC-PRS was a positive predictor of SAT and VAT; BF%-PRS was a positive predictor of BF% and SAT only. These analyses suggest that genetically driven increases in BF% strongly associate with subcutaneous rather than visceral adiposity and BF% is strongly associated with BMI but not central adiposity-associated genetic variants. How common genetic variants may contribute to observed differences in adiposity patterns between African and European ancestry individuals requires further study.
Highlights
Despite the wide adoption of body mass index (BMI), a measure that correlates well with numerous health risk factors [1], there are limitations to this metric [2]; notably, it does not differentiate between variation in fat and lean mass
Polygenic risk scores (PRS) were calculated using genome-wide association studies (GWAS)-significant variants extracted from published studies mostly representing European ancestry populations for BMI, waisthip ratio (WHR) adjusted for BMI (WHRBMIadj), waist circumference adjusted for BMI (WCBMIadj), and body fat percentage (BF%)
WC-PRS was a positive predictor of subcutaneous adiposity tissue (SAT) and visceral adiposity tissue (VAT); BF%-PRS was a positive predictor of BF% and SAT only
Summary
Despite the wide adoption of body mass index (BMI), a measure that correlates well with numerous health risk factors [1], there are limitations to this metric [2]; notably, it does not differentiate between variation in fat and lean mass This can lead to an imprecise categorization of obesity [3], and misleading inferences for cardiometabolic outcomes [4]. Since body fat is linearly associated with BMI in sedentary populations [9], a proportion of genetic variants associated with overall body mass expectedly overlap with loci linked to body fat percentage [10] This BMI-body fat mass link is known to exhibit phenotypic variability across ethnicities [11], which extends to regional distribution of fat tissue as well: in African ancestry (AA) individuals with comparable BMI metrics to those with European ancestry (EA), the proportion of visceral adiposity is lower [12, 13]. To explore the genetic underpinning of different adiposity patterns, we investigated whether genetic risk scores for well-studied adiposity phenotypes like body mass index (BMI) and waist circumference (WC) predict other, less commonly measured adiposity measures in 2420 African American individuals from the Jackson Heart Study
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