A meta-analysis and polygenic score study identifies novel genetic markers for waist-hip ratio in African populations

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity Pub Date : 2024-10-01 DOI:10.1002/oby.24123

Michael Zhong, Ebuka Onyenobi, Ayo Duomatey, Guanjie Chen, James Perry, Zhenyao Ye, ACCME Research Group as part of the H3Africa Consortium, Charles Rotimi, Clement A. Adebamowo, Adebowale Adeyemo, Sally N. Adebamowo

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Abstract

Objective

Understanding the genetic underpinnings of anthropometric traits in diverse populations is crucial for gaining insights into their biological mechanisms and potential implications for health.

Methods

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.

Results

The top loci associated with each trait in the meta-analysis were in CD36 (rs3211826 [p = 5.90 × 10⁻¹²] for WHR and rs73709003 [p = 1.75 × 10⁻¹³] for WHRadjBMI), IFI27L1 (rs59775050 [p = 2.66 × 10⁻⁰⁸] for waist circumference), INPP4B (rs2636629 [p = 1.44 × 10⁻⁰⁹] for BMI), and HMGA1 (rs6937622 [p = 1.40 × 10⁻¹⁵] for height) gene regions. A novel variant rs7797157, near GNAT3, was also significantly associated with WHR (p = 2.50 × 10⁻¹⁰) and WHRadjBMI (p = 2.66 × 10⁻¹¹). The ancestry-specific parameters for the best predictive polygenic scores were European ancestry (R² = 0.68%; p = 1.63 × 10⁻¹⁶) and multiethnic ancestry (R² = 0.06%; p = 1.29 × 10⁻⁰²) for WHR; European ancestry (R² = 1.36%; p = 2.94 × 10⁻³¹) and multiethnic ancestry (R² = 1.12%; p = 3.52 × 10⁻²⁵) for BMI; and European ancestry (R² = 3.16%; p = 2.95 × 10⁻⁷³), African ancestry (R² = 4.16%; p = 1.75 × 10⁻⁹⁶), and African and Afro-Caribbean ancestry (R² = 2.67%; p = 4.35 × 10⁻⁶²) for height.

Conclusions

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.

Abstract Image

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一项荟萃分析和多基因评分研究发现了非洲人群腰臀比的新型遗传标记。

目的：了解不同人群人体测量特征的遗传基础对于深入了解其生物机制和对健康的潜在影响至关重要：了解不同人群人体测量特征的遗传基础对于深入了解其生物学机制和对健康的潜在影响至关重要：我们利用非洲微生物组和基因组研究合作中心（ACCME）队列（n = ~11,000）进行了腰臀比（WHR）、根据体重指数调整的腰臀比（WHRadjBMI）、腰围、体重指数和身高的全基因组关联研究、荟萃分析和基因组分析，并利用非洲-美洲糖尿病（AADM）研究（n = ~5200）进行了复制和多基因评分验证。我们生成并比较了来自欧洲、非洲、非洲-加勒比和多种族血统人群的多基因得分：在荟萃分析中，与每个性状相关的最高位点分别是 CD36（rs3211826 [p = 5.90 × 10-12] 表示腰围，rs73709003 [p = 1.75 × 10-13] 表示腰围adjBMI）、IFI27L1（rs59775050 [p = 2.66 × 10-08] 表示腰围）、INPP4B（rs2636629 [p = 1.44 × 10-09] 表示体重指数）和 HMGA1（rs6937622 [p = 1.40 × 10-15] 表示身高）基因区域。GNAT3 附近的一个新变异 rs7797157 也与 WHR（p = 2.50 × 10-10）和 WHRadjBMI（p = 2.66 × 10-11）显著相关。最佳预测多基因得分的祖先特异性参数为：WHR 为欧洲祖先（R2 = 0.68%；p = 1.63 × 10-16）和多民族祖先（R2 = 0.06%；p = 1.29 × 10-02）；WHR 为欧洲祖先（R2 = 1.36%；p = 2.94 × 10-31）和多民族祖先（R2 = 1.12%; p = 3.52 × 10-25）；身高方面，欧洲血统（R2 = 3.16%; p = 2.95 × 10-73）、非洲血统（R2 = 4.16%; p = 1.75 × 10-96）以及非洲和非洲-加勒比血统（R2 = 2.67%; p = 4.35 × 10-62）：结论：发现了一个新的 WHR 基因座和每个性状的遗传信号，以及对多基因评分性能的评估，都强调了在不同人群中开展有充分动力的研究的重要性。

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来源期刊

Obesity 医学-内分泌学与代谢

CiteScore

11.70

自引率

1.40%

发文量

261

审稿时长

2-4 weeks

期刊介绍： Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.