Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Center for Research for Genomics and Global Health, National Human Genome Research Institute, Bethesda, Maryland, USA.
Obesity (Silver Spring). 2024 Nov;32(11):2175-2185. doi: 10.1002/oby.24123. Epub 2024 Oct 1.
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] for WHR and rs73709003 [p = 1.75 × 10] for WHRadjBMI), IFI27L1 (rs59775050 [p = 2.66 × 10] for waist circumference), INPP4B (rs2636629 [p = 1.44 × 10] for BMI), and HMGA1 (rs6937622 [p = 1.40 × 10] for height) gene regions. A novel variant rs7797157, near GNAT3, was also significantly associated with WHR (p = 2.50 × 10) and WHRadjBMI (p = 2.66 × 10). The ancestry-specific parameters for the best predictive polygenic scores were European ancestry (R = 0.68%; p = 1.63 × 10) and multiethnic ancestry (R = 0.06%; p = 1.29 × 10) for WHR; European ancestry (R = 1.36%; p = 2.94 × 10) and multiethnic ancestry (R = 1.12%; p = 3.52 × 10) for BMI; and European ancestry (R = 3.16%; p = 2.95 × 10), African ancestry (R = 4.16%; p = 1.75 × 10), and African and Afro-Caribbean ancestry (R = 2.67%; p = 4.35 × 10) 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.
了解不同人群中人体测量特征的遗传基础对于深入了解其生物学机制以及对健康的潜在影响至关重要。
我们使用非洲合作微生物组和基因组学研究中心（ACCME）队列（n = ~11000）进行全基因组关联研究、荟萃分析和腰围-臀围比（WHR）、WHR 调整后的 BMI（WHRadjBMI）、腰围、BMI 和身高的基因集分析，以及 polygenic 分数目标分析，并使用非洲裔美国糖尿病研究（AADM）研究（n = ~5200）进行复制和 polygenic 分数验证。我们从欧洲、非洲、非裔加勒比和多种族人群中生成和比较了 polygenic 分数。
荟萃分析中与每个特征相关的最高基因座位于 CD36（rs3211826 [p = 5.90 × 10] 与 WHR 和 rs73709003 [p = 1.75 × 10] 与 WHRadjBMI）、IFI27L1（rs59775050 [p = 2.66 × 10] 与腰围）、INPP4B（rs2636629 [p = 1.44 × 10] 与 BMI）和 HMGA1（rs6937622 [p = 1.40 × 10] 与身高）基因区域。一个新的变体 rs7797157，靠近 GNAT3，也与 WHR（p = 2.50 × 10）和 WHRadjBMI（p = 2.66 × 10）显著相关。最佳预测 polygenic 分数的种族特异性参数为欧洲血统（R = 0.68%；p = 1.63 × 10）和多种族血统（R = 0.06%；p = 1.29 × 10）与 WHR；欧洲血统（R = 1.36%；p = 2.94 × 10）和多种族血统（R = 1.12%；p = 3.52 × 10）与 BMI；欧洲血统（R = 3.16%；p = 2.95 × 10）、非洲血统（R = 4.16%；p = 1.75 × 10）和非洲裔加勒比血统（R = 2.67%；p = 4.35 × 10）与身高。
发现 WHR 的新基因座和每个特征的遗传信号，以及评估多基因评分表现，强调了在不同人群中进行功能强大的研究的重要性。
