A meta-analysis and polygenic score study identifies novel genetic markers for waist-hip ratio in African populations.
meta_analysis · Level I
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- Record sourced from PubMed, PMID 39351966.
- Also identified by DOI 10.1002/oby.24123 and PMC identifier 11692486.
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Abstract
Understanding the genetic underpinnings of anthropometric traits in diverse populations is crucial for gaining insights into their biological mechanisms and potential implications for health. We conducted a genome-wide association study, meta-analysis, and gene set analysis of waist-hip ratio (WHR), WHR adjusted for BMI (WHRadjBMI), waist circumference, BMI, and height using the African Collaborative Center for Microbiome and Genomics Research (ACCME) cohort (n = ~11,000) for discovery and polygenic score target analyses and the Africa America Diabetes Mellitus (AADM) study (n = ~5200) for replication and polygenic score validation. We generated and compared polygenic scores from European, African, Afro-Caribbean, and multiethnic ancestry populations. The top loci associated with each trait in the meta-analysis were in CD36 (rs3211826 [p = 5.90 × 10<sup>-12</sup>] for WHR and rs73709003 [p = 1.75 × 10<sup>-13</sup>] for WHRadjBMI), IFI27L1 (rs59775050 [p = 2.66 × 10<sup>-08</sup>] for waist circumference), INPP4B (rs2636629 [p = 1.44 × 10<sup>-09</sup>] for BMI), and HMGA1 (rs6937622 [p = 1.40 × 10<sup>-15</sup>] for height) gene regions. A novel variant rs7797157, near GNAT3, was also significantly associated with WHR (p = 2.50 × 10<sup>-10</sup>) and WHRadjBMI (p = 2.66 × 10<sup>-11</sup>). The ancestry-specific parameters for the best predictive polygenic scores were European ancestry (R<sup>2</sup> = 0.68%; p = 1.63 × 10<sup>-16</sup>) and multiethnic ancestry (R<sup>2</sup> = 0.06%; p = 1.29 × 10<sup>-02</sup>) for WHR; European ancestry (R<sup>2</sup> = 1.36%; p = 2.94 × 10<sup>-31</sup>) and multiethnic ancestry (R<sup>2</sup> = 1.12%; p = 3.52 × 10<sup>-25</sup>) for BMI; and European ancestry (R<sup>2</sup> = 3.16%; p = 2.95 × 10<sup>-73</sup>), African ancestry (R<sup>2</sup> = 4.16%; p = 1.75 × 10<sup>-96</sup>), and African and Afro-Caribbean ancestry (R<sup>2</sup> = 2.67%; p = 4.35 × 10<sup>-62</sup>) for height. The discovery of a novel locus for WHR and genetic signals for each trait and the assessment of polygenic score performance underscore the importance of conducting well-powered studies in diverse populations.
Medical subject headings
- Waist-Hip Ratio
- Genome-Wide Association Study
- Multifactorial Inheritance
- Body Mass Index
- Black People