WHOLE GENOME SEQUENCING ANALYSIS OF BODY MASS INDEX IDENTIFIES NOVEL AFRICAN ANCESTRY-SPECIFIC RISK ALLELE.

Journal

medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986

Informations de publication

Date de publication:
22 Aug 2023
Historique:
pubmed: 4 9 2023
medline: 4 9 2023
entrez: 4 9 2023
Statut: epublish

Résumé

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 (

Identifiants

DOI: 10.1101/2023.08.21.23293271 PMID: 37662265 PMC: PMC10473809
pubmed: 37662265
doi: 10.1101/2023.08.21.23293271
pmc: PMC10473809
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NHLBI NIH HHS
ID : U01 HL054472
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA203654
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL054509
Pays : United States
Organisme : NHLBI NIH HHS
ID : F32 HL085989
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL072524
Pays : United States
Organisme : BLRD VA
ID : I01 BX003340
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM109036
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA134294
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009088
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007055
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK122503
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197449
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL104135
Pays : United States
Organisme : BLRD VA
ID : I01 BX004821
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133040
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR048797
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007416
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL120393
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL089897
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL113338
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG058921
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142302
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK110113
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS058700
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107786
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL119443
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI114555
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL089856
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL129982
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL067348
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL104608
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132476
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL136928
Pays : United States
Organisme : NCRR NIH HHS
ID : M01 RR007122
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR002490
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142825
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124097
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL093093
Pays : United States
Organisme : BLRD VA
ID : I01 BX003362
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL068959
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL072507
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK071891
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL132825
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG010297
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL054495
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL055673
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL092301
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL054473
Pays : United States

Déclaration de conflit d'intérêts

Disclosures/Competing Interests DLD received grants from Bayer and honoraria from Novartis. BDHo receives grant support from Bayer and has received an honorarium from AstraZeneca for an educational lecture. CJO is employed by Novartis Institute of Biomedical Research, Cambridge MA KCB is an employee of Tempus. BMPs serve on the TOPMed Steering Committee. LMR is a consultant for the TOPMed Administrative Coordinating Center (through Westat). XLin is a consultant of AbbVie Pharmaceuticals and Verily Life Sciences.

Auteurs

Xinruo Zhang (X)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Jennifer A Brody (JA)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.

Mariaelisa Graff (M)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Heather M Highland (HM)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Nathalie Chami (N)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Hanfei Xu (H)

Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.

Zhe Wang (Z)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Kendra Ferrier (K)

Division of Biomedical Informatics and Personalized Medicine, School of Medicine University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.

Geetha Chittoor (G)

Population Health Sciences, Geisinger, Danville, PA, USA.

Navya S Josyula (NS)

Population Health Sciences, Geisinger, Danville, PA, USA.

Xihao Li (X)

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Zilin Li (Z)

Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA.

Matthew A Allison (MA)

Department of Family Medicine, Division of Preventive Medicine, The University of California San Diego, La Jolla, CA, USA.

Diane M Becker (DM)

Department of Medicine, General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Lawrence F Bielak (LF)

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.

Joshua C Bis (JC)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.

Meher Preethi Boorgula (MP)

Department of Medicine, School of Medicine, University of Colorado, Aurora, CO, USA.

Donald W Bowden (DW)

Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Jai G Broome (JG)

Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA, USA.

Erin J Buth (EJ)

Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Christopher S Carlson (CS)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Kyong-Mi Chang (KM)

The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Sameer Chavan (S)

Department of Medicine, School of Medicine, University of Colorado, Aurora, CO, USA.

Yen-Feng Chiu (YF)

Institute of Population Health Sciences, National Health Research Institutes, Taipei, Taiwan.

Lee-Ming Chuang (LM)

Department of Internal Medicine, Division of Metabolism/Endocrinology, National Taiwan University Hospital, Taipei, Taiwan.

Matthew P Conomos (MP)

Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Dawn L DeMeo (DL)

Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Margaret Du (M)

Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Ravindranath Duggirala (R)

Life Sciences, College of Arts and Sciences, Texas A&M University-San Antonio, San Antonio, TX, USA.

Celeste Eng (C)

Department of Medicine, Lung Biology Center, University of California, San Francisco, San Francisco, CA, USA.

Alison E Fohner (AE)

Epidemiology, Institute of Public Health Genetics, School of Public Health, University of Washington, Seattle, WA, USA.

Barry I Freedman (BI)

Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Melanie E Garrett (ME)

Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.

Xiuqing Guo (X)

Department of Pediatrics, Genomic Outcomes, 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.

Chris Haiman (C)

Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Benjamin D Heavner (BD)

Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Bertha Hidalgo (B)

Department of Epidemiology, School of Public Health, University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA.

James E Hixson (JE)

Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Yuk-Lam Ho (YL)

Veterans Affairs Boston Healthcare System, Boston, MA, USA.

Brian D Hobbs (BD)

Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Donglei Hu (D)

Department of Medicine, Lung Biology Center, University of California, San Francisco, San Francisco, CA, USA.

Qin Hui (Q)

Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
Atlanta VA Health Care System, Decatur, GA, USA.

Chii-Min Hwu (CM)

Department of Medicine, Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan, Taiwan.

Rebecca D Jackson (RD)

Endocrinology, Ohio State University, Columbus, OH, USA.

Deepti Jain (D)

Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Rita R Kalyani (RR)

Department of Medicine, Endocrinology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Sharon L R Kardia (SLR)

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.

Tanika N Kelly (TN)

Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.

Ethan M Lange (EM)

Division of Biomedical Informatics and Personalized Medicine, School of Medicine University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.

Michael LeNoir (M)

Department of Pediatrics, Bay Area Pediatrics, Oakland, CA, USA.

Changwei Li (C)

Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.

Loic Le Marchand (LL)

Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.

Merry-Lynn N McDonald (MN)

Department of Medicine, Pulmonary, Allergy and Critical Care, University of Alabama at Birmingham, Birmingham, AL, USA.

Caitlin P McHugh (CP)

Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Alanna C Morrison (AC)

Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Take Naseri (T)

Ministry of Health, Government of Samoa, Apia, Samoa.

Jeffrey O'Connell (J)

Department of Medicine, Program for Personalized and Genomic Medicine, University of Maryland, Baltimore, MD, USA.

Christopher J O'Donnell (CJ)

Veterans Affairs Boston Healthcare System, Boston, MA, USA.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Nicholette D Palmer (ND)

Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.

James S Pankow (JS)

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

James A Perry (JA)

Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA.

Ulrike Peters (U)

Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.

Michael H Preuss (MH)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

D C Rao (DC)

Division of Biostatistics, Washington University in St. Louis, St. Louis, MO, USA.

Elizabeth A Regan (EA)

Department of Medicine, Rheumatology, National Jewish Health, Denver, CO, USA.

Sefuiva M Reupena (SM)

Lutia I Puava Ae Mapu I Fagalele, Apia, Samoa.

Dan M Roden (DM)

Medicine, Pharmacology, and Biomedical Informatics, Clinical Pharmacology and Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Jose Rodriguez-Santana (J)

Centro de Neumologia Pediatrica, San Juan, PR, USA.

Colleen M Sitlani (CM)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.

Jennifer A Smith (JA)

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.

Hemant K Tiwari (HK)

Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA.

Ramachandran S Vasan (RS)

Department of Medicine, School of Medicine, Boston University, Boston, MA, USA.

Zeyuan Wang (Z)

Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.

Daniel E Weeks (DE)

Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.

Jennifer Wessel (J)

Department of Epidemiology, Indiana University, Indianapolis, IN, USA.
Department of Medicine, Indiana University, Indianapolis, IN, USA.
Diabaetes Translational Research Center, Indiana University, Indianapolis, IN, USA.

Kerri L Wiggins (KL)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.

Lynne R Wilkens (LR)

Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.

Peter W F Wilson (PWF)

Atlanta VA Health Care System, Decatur, GA, USA.
Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Lisa R Yanek (LR)

Department of Medicine, General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Zachary T Yoneda (ZT)

Department of Medicine, Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Wei Zhao (W)

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.

Sebastian Zöllner (S)

Department of Biostatistics, Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.

Donna K Arnett (DK)

Department of Epidemiology, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA.

Allison E Ashley-Koch (AE)

Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.

Kathleen C Barnes (KC)

Department of Medicine, School of Medicine, University of Colorado, Aurora, CO, USA.

John Blangero (J)

Human Genetics and South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.

Eric Boerwinkle (E)

Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Esteban G Burchard (EG)

Bioengineering and Therapeutic Sciences and Medicine, Lung Biology Center, University of California, San Francisco, San Francisco, CA, USA.

April P Carson (AP)

Department of Medicine, University of Mississippi, Jackson, MI, USA.

Daniel I Chasman (DI)

Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.

Yii-Der Ida Chen (YI)

Department of Medical Genetics, Genomic Outcomes, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.

Joanne E Curran (JE)

Department of Human Genetics and South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.

Myriam Fornage (M)

Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Victor R Gordeuk (VR)

Department of Medicine, School of Medicine, University of Illinois at Chicago, Chicago, IL, USA.

Jiang He (J)

Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.

Susan R Heckbert (SR)

Department of Epidemiology, University of Washington, Seattle, WA, USA.
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.

Lifang Hou (L)

Northwestern University, Chicago, IL, USA.

Marguerite R Irvin (MR)

Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA.

Charles Kooperberg (C)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Ryan L Minster (RL)

Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.

Braxton D Mitchell (BD)

Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland, Baltimore, MD, USA.

Mehdi Nouraie (M)

Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Bruce M Psaty (BM)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Department of Epidemiology, University of Washington, Seattle, WA, USA.
Department of Health Systems and Population Health, University of Washington, Seattle, WA, USA.

Laura M Raffield (LM)

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Alexander P Reiner (AP)

Department of Epidemiology, University of Washington, Seattle, WA, USA.

Stephen S Rich (SS)

Public Health Science, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.

Jerome I Rotter (JI)

Department of Pediatrics, Genomic Outcomes, 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.

M Benjamin Shoemaker (MB)

Department of Medicine, Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Nicholas L Smith (NL)

Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA, USA.
Seattle Epidemiologic Research and Information Center, Office of Research and Development, Department of Veterans Affairs, Seattle, WA, USA.

Kent D Taylor (KD)

Department of Pediatrics, Genomic Outcomes, 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 (MJ)

Department of Medicine, Hematology, Duke University Medical Center, Durham, NC, USA.

Scott T Weiss (ST)

Department of Medicine, Channing Division of Network Medicine, Harvard Medical School, Boston, MA, USA.

Yingze Zhang (Y)

Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Nancy Heard-Costa (N)

Framingham Heart Study, School of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.

Yan V Sun (YV)

Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
Atlanta VA Health Care System, Decatur, GA, USA.

Xihong Lin (X)

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Statistics, Harvard University, Boston, MA, USA.

L Adrienne Cupples (L)

Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.

Leslie A Lange (LA)

Division of Biomedical Informatics and Personalized Medicine, School of Medicine University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.

Ching-Ti Liu (CT)

Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.

Ruth J F Loos (RJF)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.

Kari E North (KE)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Anne E Justice (AE)

Population Health Sciences, Geisinger, Danville, PA, USA.

Classifications MeSH