Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele
Abstract
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.
Article Details
Authors (124)
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
Department of Biostatistics
Zilin Li
Matthew A. Allison
Diane M. Becker
Lawrence F. Bielak
Joshua C. Bis
Meher Preethi Boorgula
University of Colorado at Denver, Denver, CO, USA.
Donald W. Bowden
Jai G. Broome
Erin J. Buth
Christopher S. Carlson
Kyong-Mi Chang
Sameer Chavan
University of Colorado at Denver, Denver, CO, USA.
Yen-Feng Chiu
Lee-Ming Chuang
National Taiwan University, Taipei, Taiwan (Province of China).
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
University of Washington, Seattle, WA, USA.
Rita R. Kalyani
Sharon L. R. Kardia
Tanika N. Kelly
Ethan M. Lange
Michael LeNoir
Changwei Li
Merry-Lynn N. McDonald
Caitlin P. McHugh
Alanna C. Morrison
Take Naseri
Loic Le Marchand
Jeffrey O’Connell
Christopher J. O’Donnell
Nicholette D. Palmer
James S. Pankow
James A. Perry
Ulrike Peters
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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
Framingham Heart Study, National Heart, Lung, and Blood Institute, National Institutes of Health and Boston University, Framingham, MA, USA.
Zeyuan Wang
Daniel E. Weeks
Jennifer Wessel
Indiana University, Indianapolis, IN, USA.
Kerri L. Wiggins
Lynne R. Wilkens
Peter W. F. Wilson
Lisa R. Yanek
Zachary T. Yoneda
Wei Zhao
Sebastian Zöllner
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
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
Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Ryan L. Minster
Braxton D. Mitchell
Mehdi Nouraie
Bruce M. Psaty
Laura M. Raffield
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alexander P. Reiner
Stephen S. Rich
Department of Genome Sciences, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Jerome I. Rotter
M. Benjamin Shoemaker
Nicholas L. Smith
Kent D. Taylor
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Marilyn J. Telen
Scott T. Weiss
Yingze Zhang
Nancy Heard-Costa
Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, USA.
Yan V. Sun
Xihong Lin
L. Adrienne Cupples
Framingham Heart Study, National Heart, Lung, and Blood Institute, National Institutes of Health and Boston University, Framingham, MA, USA.
Leslie A. Lange
Ching-Ti Liu
Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
Ruth J. F. Loos
Kari E. North
Anne E. Justice