Genetic underpinnings of regional adiposity distribution in African Americans: Assessments from the Jackson Heart Study

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

Neuroanatomical correlates of genetic risk for obesity in children

“…We assessed genetic risk for obesity using BMI-PRS, which allows us to calculate each individual’s PRS from a well-powered, recent BMI GWAS [ 18 ]. BMI-PRS is reflective of a more general risk for obesity and cardiometabolic comorbidities and correlates well with body fat percentage [ 18 , 46 , 47 ]. BMI-PRS was calculated using PRSice-2 [ 48 ] with pruning and thresholding of BMI GWAS summary statistics from an independent data sample ( https://www.ebi.ac.uk/gwas/downloads/summary-statistics ) [ 18 ].…”

Associations of cardiometabolic polygenic risk scores with cardiovascular disease in African Americans

“…SNPs with minor allele frequency (MAF) ≥ 1%, a call rate ≥ 90%, and a Hardy-Weinberg Equilibrium (HWE) P-value > 10 − 6 were used for imputation to the 1000 Genomes reference panel. [33] The rst 10 principal components were estimated to represent global ancestry based on linkage-disequilibrium pruned set of SNPs with MAF > 0.05. [34] Outliers based on the principal component scores for global ancestry, sample swaps, duplicates, and one of each pair of monozygotic twins were excluded.…”

“…Participants with a mismatch between pedigree vs genetic sex were also removed. [33] Out of N = 47,101,766 imputed SNPs in the JHS, the present analysis included N = 9,360,683 SNPs with MAF > 0.05%, genotype call rate ≥ 90% and HWE P-value > 10 − 6 .…”