Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-04-11 DOI:10.1038/s41467-025-58420-2

Xinruo Zhang, Jennifer A. Brody, Mariaelisa Graff, Heather M. Highland, Nathalie Chami, Hanfei Xu, Zhe Wang, Kendra R. Ferrier, Geetha Chittoor, Navya Shilpa Josyula, Mariah Meyer, Shreyash Gupta, Xihao Li, Zilin Li, Matthew A. Allison, Diane M. Becker, Lawrence F. Bielak, Joshua C. Bis, Meher Preethi Boorgula, Donald W. Bowden, Jai G. Broome, Erin J. Buth, Christopher S. Carlson, Kyong-Mi Chang, Sameer Chavan, Yen-Feng Chiu, Lee-Ming Chuang, Matthew P. Conomos, Dawn L. DeMeo, Mengmeng Du, Ravindranath Duggirala, Celeste Eng, Alison E. Fohner, Barry I. Freedman, Melanie E. Garrett, Xiuqing Guo, Chris Haiman, Benjamin D. Heavner, Bertha Hidalgo, James E. Hixson, Yuk-Lam Ho, Brian D. Hobbs, Donglei Hu, Qin Hui, Chii-Min Hwu, Rebecca D. Jackson, Deepti Jain, Rita R. Kalyani, Sharon L. R. Kardia, Tanika N. Kelly, Ethan M. Lange, Michael LeNoir, Changwei Li, Loic Le Marchand, Merry-Lynn N. McDonald, Caitlin P. McHugh, Alanna C. Morrison, Take Naseri, Jeffrey O’Connell, Christopher J. O’Donnell, Nicholette D. Palmer, James S. Pankow, James A. Perry, Ulrike Peters, Michael H. Preuss, D. C. Rao, Elizabeth A. Regan, Sefuiva M. Reupena, Dan M. Roden, Jose Rodriguez-Santana, Colleen M. Sitlani, Jennifer A. Smith, Hemant K. Tiwari, Ramachandran S. Vasan, Zeyuan Wang, Daniel E. Weeks, Jennifer Wessel, Kerri L. Wiggins, Lynne R. Wilkens, Peter W. F. Wilson, Lisa R. Yanek, Zachary T. Yoneda, Wei Zhao, Sebastian Zöllner, Donna K. Arnett, Allison E. Ashley-Koch, Kathleen C. Barnes, John Blangero, Eric Boerwinkle, Esteban G. Burchard, April P. Carson, Daniel I. Chasman, Yii-Der Ida Chen, Joanne E. Curran, Myriam Fornage, Victor R. Gordeuk, Jiang He, Susan R. Heckbert, Lifang Hou, Marguerite R. Irvin, Charles Kooperberg, Ryan L. Minster, Braxton D. Mitchell, Mehdi Nouraie, Bruce M. Psaty, Laura M. Raffield, Alexander P. Reiner, Stephen S. Rich, Jerome I. Rotter, M. Benjamin Shoemaker, Nicholas L. Smith, Kent D. Taylor, Marilyn J. Telen, Scott T. Weiss, Yingze Zhang, Nancy Heard-Costa, Yan V. Sun, Xihong Lin, L. Adrienne Cupples, Leslie A. Lange, Ching-Ti Liu, Ruth J. F. Loos, Kari E. North, Anne E. Justice

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引用次数: 0

Abstract

Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P < 5 × 10⁻⁹), including two secondary signals. Notably, we identified and replicated a novel low-frequency single nucleotide polymorphism (SNP) in MTMR3 that was common in individuals of African descent. Using a diverse study population, we further identified two novel secondary signals in known BMI loci and pinpointed two likely causal variants in the POC5 and DMD loci. Our work demonstrates the benefits of combining WGS and diverse cohorts in expanding current catalog of variants and genes confer risk for obesity, bringing us one step closer to personalized medicine.

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身体质量指数的全基因组测序分析发现了新的非洲血统特异性风险等位基因

肥胖是与高死亡率相关的重大公共卫生危机。以前的全基因组关联研究（GWAS）调查身体质量指数（BMI）很大程度上依赖于来自欧洲个体的输入数据。这项研究利用了来自反式精准医学组学（TOPMed）项目的88,873名参与者的全基因组测序（WGS）数据，其中51%来自非欧洲人群。我们发现了18个bmi相关信号（P < 5 × 10−9），包括两个次要信号。值得注意的是，我们在MTMR3中发现并复制了一种新的低频单核苷酸多态性（SNP），这种多态性在非洲人后裔中很常见。通过不同的研究人群，我们进一步在已知的BMI基因座中确定了两个新的次要信号，并在POC5和DMD基因座中确定了两个可能的因果变异。我们的工作证明了将WGS和不同队列结合在一起的好处，可以扩大当前的变异和肥胖风险基因目录，使我们更接近个性化医疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.