Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele.
Journal
Nature communications
Journal Volume
16
Journal Issue
1
Start Page
3470
ISSN
2041-1723
Date Issued
2025-04-11
Author(s)
Zhang, Xinruo
Brody, Jennifer A
Graff, Mariaelisa
Highland, Heather M
Chami, Nathalie
Xu, Hanfei
Wang, Zhe
Ferrier, Kendra R
Chittoor, Geetha
Josyula, Navya Shilpa
Meyer, Mariah
Gupta, Shreyash
Li, Xihao
Li, Zilin
Allison, Matthew A
Becker, Diane M
Bielak, Lawrence F
Bis, Joshua C
Boorgula, Meher Preethi
Bowden, Donald W
Broome, Jai G
Buth, Erin J
Carlson, Christopher S
Chang, Kyong-Mi
Chavan, Sameer
Chiu, Yen-Feng
Conomos, Matthew P
DeMeo, Dawn L
Du, Mengmeng
Duggirala, Ravindranath
Eng, Celeste
Fohner, Alison E
Freedman, Barry I
Garrett, Melanie E
Guo, Xiuqing
Haiman, Chris
Heavner, Benjamin D
Hidalgo, Bertha
Hixson, James E
Ho, Yuk-Lam
Hobbs, Brian D
Hu, Donglei
Hui, Qin
Hwu, Chii-Min
Jackson, Rebecca D
Jain, Deepti
Kalyani, Rita R
Kardia, Sharon L R
Kelly, Tanika N
Lange, Ethan M
LeNoir, Michael
Li, Changwei
Le Marchand, Loic
McDonald, Merry-Lynn N
McHugh, Caitlin P
Morrison, Alanna C
Naseri, Take
O'Connell, Jeffrey
O'Donnell, Christopher J
Palmer, Nicholette D
Pankow, James S
Perry, James A
Peters, Ulrike
Preuss, Michael H
Rao, D C
Regan, Elizabeth A
Reupena, Sefuiva M
Roden, Dan M
Rodriguez-Santana, Jose
Sitlani, Colleen M
Smith, Jennifer A
Tiwari, Hemant K
Vasan, Ramachandran S
Wang, Zeyuan
Weeks, Daniel E
Wessel, Jennifer
Wiggins, Kerri L
Wilkens, Lynne R
Wilson, Peter W F
Yanek, Lisa R
Yoneda, Zachary T
Zhao, Wei
Zöllner, Sebastian
Arnett, Donna K
Ashley-Koch, Allison E
Barnes, Kathleen C
Blangero, John
Boerwinkle, Eric
Burchard, Esteban G
Carson, April P
Chasman, Daniel I
Ida Chen, Yii-Der
Curran, Joanne E
Fornage, Myriam
Gordeuk, Victor R
He, Jiang
Heckbert, Susan R
Hou, Lifang
Irvin, Marguerite R
Kooperberg, Charles
Minster, Ryan L
Mitchell, Braxton D
Nouraie, Mehdi
Psaty, Bruce M
Raffield, Laura M
Reiner, Alexander P
Rich, Stephen S
Rotter, Jerome I
Benjamin Shoemaker, M
Smith, Nicholas L
Taylor, Kent D
Telen, Marilyn J
Weiss, Scott T
Zhang, Yingze
Heard-Costa, Nancy
Sun, Yan V
Lin, Xihong
Cupples, L Adrienne
Lange, Leslie A
Liu, Ching-Ti
Loos, Ruth J F
North, Kari E
Justice, Anne E
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), 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.
SDGs
Type
journal article