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

被引：0

作者：

Xinruo Zhang ^{[1
]}

Jennifer A. Brody ^{[2
]}

Mariaelisa Graff ^{[1
]}

Heather M. Highland ^{[1
]}

Nathalie Chami ^{[3
]}

Hanfei Xu ^{[4
]}

Zhe Wang ^{[5
]}

Kendra R. Ferrier ^{[3
]}

Geetha Chittoor ^{[6
]}

Navya Shilpa Josyula ^{[7
]}

Mariah Meyer ^{[7
]}

Shreyash Gupta ^{[6
]}

Xihao Li ^{[7
]}

Zilin Li ^{[8
]}

Matthew A. Allison ^{[9
]}

Diane M. Becker ^{[10
]}

Lawrence F. Bielak ^{[11
]}

Joshua C. Bis ^{[12
]}

Meher Preethi Boorgula ^{[13
]}

Donald W. Bowden ^{[14
]}

Jai G. Broome ^{[15
]}

Erin J. Buth ^{[2
]}

Christopher S. Carlson ^{[16
]}

Kyong-Mi Chang ^{[17
]}

Sameer Chavan ^{[18
]}

Yen-Feng Chiu ^{[19
]}

Lee-Ming Chuang ^{[18
]}

Matthew P. Conomos ^{[20
]}

Dawn L. DeMeo ^{[21
]}

Mengmeng Du ^{[22
]}

Ravindranath Duggirala ^{[16
]}

Celeste Eng ^{[23
]}

Alison E. Fohner ^{[24
]}

Barry I. Freedman ^{[18
]}

Melanie E. Garrett ^{[25
]}

Xiuqing Guo ^{[26
]}

Chris Haiman ^{[27
]}

Benjamin D. Heavner ^{[28
]}

Bertha Hidalgo ^{[29
]}

James E. Hixson ^{[30
]}

Yuk-Lam Ho ^{[31
]}

Brian D. Hobbs ^{[32
]}

Donglei Hu ^{[33
]}

Qin Hui ^{[34
]}

Chii-Min Hwu ^{[18
]}

Rebecca D. Jackson ^{[35
]}

Deepti Jain ^{[36
]}

Rita R. Kalyani ^{[37
]}

Sharon L. R. Kardia ^{[25
]}

Tanika N. Kelly ^{[38
]}

机构：

[1] University of North Carolina at Chapel Hill,Department of Epidemiology, Gillings School of Global Public Health

[2] University of Washington,Cardiovascular Health Research Unit, Department of Medicine

[3] Icahn School of Medicine at Mount Sinai,The Charles Bronfman Institute for Personalized Medicine

[4] Icahn School of Medicine at Mount Sinai,The Mindich Child Health and Development Institute

[5] Boston University,Department of Biostatistics, School of Public Health

[6] University of Colorado School of Medicine,Division of Biomedical Informatics and Personalized Medicine

[7] Anschutz Medical Campus,Population Health Sciences

[8] Geisinger,Department of Biostatistics

[9] Harvard T.H. Chan School of Public Health,Department of Biostatistics, Gillings School of Global Public Health

[10] University of North Carolina at Chapel Hill,Department of Genetics, School of Medicine

[11] University of North Carolina at Chapel Hill,Biostatistics and Health Data Science

[12] Indiana University School of Medicine,School of Mathematics and Statistics and KLAS

[13] Northeast Normal University,Department of Family Medicine, Division of Preventive Medicine

[14] The University of California San Diego,Department of Medicine, General Internal Medicine

[15] Johns Hopkins University School of Medicine,Department of Epidemiology, School of Public Health

[16] University of Michigan,Department of Medicine

[17] University of Colorado School of Medicine,Department of Biochemistry

[18] Wake Forest School of Medicine,Department of Biostatistics, School of Public Health

[19] University of Washington,Department of Medicine, Division of Medical Genetics

[20] University of Washington,Division of Public Health Sciences

[21] Fred Hutchinson Cancer Center,Institute of Population Health Sciences

[22] The Corporal Michael J. Crescenz VA Medical Center,Department of Internal Medicine, Division of Metabolism/Endocrinology

[23] University of Pennsylvania Perelman School of Medicine,Department of Medicine, Channing Division of Network Medicine, Brigham and Women’s Hospital

[24] National Health Research Institutes,Department of Epidemiology and Biostatistics

[25] National Taiwan University Hospital,Life Sciences, College of Arts and Sciences

[26] Harvard Medical School,Department of Health and Behavioral Sciences, College of Arts and Sciences

[27] Memorial Sloan Kettering Cancer Center,Department of Medicine, Lung Biology Center

[28] Texas A&M University-San Antonio,Epidemiology, Institute of Public Health Genetics, School of Public Health

[29] Texas A&M University-San Antonio,Internal Medicine, Section on Nephrology

[30] University of California,Duke Molecular Physiology Institute

[31] San Francisco,Department of Pediatrics, Genomic Outcomes, The Institute for Translational Genomics and Population Sciences, Department of Pediatrics

[32] University of Washington,Preventive Medicine, Keck School of Medicine

[33] Wake Forest School of Medicine,Department of Epidemiology, School of Public Health

[34] Duke University Medical Center,Department of Epidemiology, School of Public Health

[35] The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center,Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital

[36] University of Southern California,Department of Epidemiology

[37] University of Alabama at Birmingham School of Public Health,Department of Medicine, Division of Endocrinology and Metabolism

[38] UTHealth Houston,Endocrinology

[39] Veterans Affairs Boston Healthcare System,Department of Medicine, Endocrinology

[40] Harvard Medical School,Department of Epidemiology, School of Public Health and Tropical Medicine

[41] Emory University Rollins School of Public Health,Department of Pediatrics

[42] Atlanta VA Health Care System,Epidemiology Program

[43] Taipei Veterans General Hospital,Department of Medicine, Pulmonary, Allergy and Critical Care

[44] Ohio State University,Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health

[45] Johns Hopkins University School of Medicine,International Health Institute

[46] Tulane University,Department of Medicine, Program for Personalized and Genomic Medicine

[47] Bay Area Pediatrics,Department of Medicine, Brigham and Women’s Hospital

[48] University of Hawaii Cancer Center,Division of Epidemiology and Community Health, School of Public Health

[49] University of Alabama at Birmingham,Department of Medicine, School of Medicine

[50] The University of Texas Health Science Center at Houston,Center for Biostatistics and Data Science

来源：

Nature Communications | / 16卷 / 1期

关键词：

D O I：

10.1038/s41467-025-58420-2

中图分类号：

学科分类号：

摘要：

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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