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

Autor:	Zhang X; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Brody JA; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA., Graff M; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Highland HM; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Chami N; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Xu H; Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA., Wang Z; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Ferrier K; Division of Biomedical Informatics and Personalized Medicine, School of Medicine University of Colorado, Anschutz Medical Campus, Aurora, CO, USA., Chittoor G; Population Health Sciences, Geisinger, Danville, PA, USA., Josyula NS; Population Health Sciences, Geisinger, Danville, PA, USA., Li X; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Li Z; Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA., Allison MA; Department of Family Medicine, Division of Preventive Medicine, The University of California San Diego, La Jolla, CA, USA., Becker DM; Department of Medicine, General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Bielak LF; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Bis JC; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA., Boorgula MP; Department of Medicine, School of Medicine, University of Colorado, Aurora, CO, USA., Bowden DW; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA., 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., Buth EJ; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA., Carlson CS; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Chang KM; The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.; University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Chavan S; Department of Medicine, School of Medicine, University of Colorado, Aurora, CO, USA., Chiu YF; Institute of Population Health Sciences, National Health Research Institutes, Taipei, Taiwan., Chuang LM; Department of Internal Medicine, Division of Metabolism/Endocrinology, National Taiwan University Hospital, Taipei, Taiwan., Conomos MP; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA., DeMeo DL; Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Du M; Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Duggirala R; Life Sciences, College of Arts and Sciences, Texas A&M University-San Antonio, San Antonio, TX, USA., Eng C; Department of Medicine, Lung Biology Center, University of California, San Francisco, San Francisco, CA, USA., Fohner AE; Epidemiology, Institute of Public Health Genetics, School of Public Health, University of Washington, Seattle, WA, USA., Freedman BI; Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA., Garrett ME; Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA., 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., Haiman C; Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Heavner BD; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA., Hidalgo B; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA., 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., Ho YL; Veterans Affairs Boston Healthcare System, Boston, MA, USA., 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., Hu D; Department of Medicine, Lung Biology Center, University of California, San Francisco, San Francisco, CA, USA., Hui Q; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.; Atlanta VA Health Care System, Decatur, GA, USA., Hwu CM; Department of Medicine, Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan, Taiwan., Jackson RD; Endocrinology, Ohio State University, Columbus, OH, USA., Jain D; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA., Kalyani RR; Department of Medicine, Endocrinology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Kardia SLR; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Kelly TN; Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA., Lange EM; Division of Biomedical Informatics and Personalized Medicine, School of Medicine University of Colorado, Anschutz Medical Campus, Aurora, CO, USA., LeNoir M; Department of Pediatrics, Bay Area Pediatrics, Oakland, CA, USA., Li C; Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA., Marchand LL; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA., McDonald MN; Department of Medicine, Pulmonary, Allergy and Critical Care, University of Alabama at Birmingham, Birmingham, AL, USA., McHugh CP; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA., 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., Naseri T; Ministry of Health, Government of Samoa, Apia, Samoa., O'Connell J; Department of Medicine, Program for Personalized and Genomic Medicine, University of Maryland, Baltimore, MD, USA., 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., Palmer ND; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA., Pankow JS; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA., Perry JA; Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA., Peters U; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA., Preuss MH; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Rao DC; Division of Biostatistics, Washington University in St. Louis, St. Louis, MO, USA., Regan EA; Department of Medicine, Rheumatology, National Jewish Health, Denver, CO, USA., Reupena SM; Lutia I Puava Ae Mapu I Fagalele, Apia, Samoa., Roden DM; Medicine, Pharmacology, and Biomedical Informatics, Clinical Pharmacology and Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Rodriguez-Santana J; Centro de Neumologia Pediatrica, San Juan, PR, USA., Sitlani CM; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA., 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., Tiwari HK; Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA., Vasan RS; Department of Medicine, School of Medicine, Boston University, Boston, MA, USA., Wang Z; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA., 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., 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., Wiggins KL; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA., Wilkens LR; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA., Wilson PWF; Atlanta VA Health Care System, Decatur, GA, USA.; Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Yanek LR; Department of Medicine, General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Yoneda ZT; Department of Medicine, Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., 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., Zöllner S; Department of Biostatistics, Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA., Arnett DK; Department of Epidemiology, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA., Ashley-Koch AE; Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA., Barnes KC; Department of Medicine, School of Medicine, University of Colorado, Aurora, CO, USA., Blangero J; Human Genetics and South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA., 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., Burchard EG; Bioengineering and Therapeutic Sciences and Medicine, Lung Biology Center, University of California, San Francisco, San Francisco, CA, USA., Carson AP; Department of Medicine, University of Mississippi, Jackson, MI, USA., Chasman DI; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Chen YI; Department of Medical Genetics, Genomic Outcomes, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA., 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., 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., Gordeuk VR; Department of Medicine, School of Medicine, University of Illinois at Chicago, Chicago, IL, USA., He J; Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA., Heckbert SR; Department of Epidemiology, University of Washington, Seattle, WA, USA.; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA., Hou L; Northwestern University, Chicago, IL, USA., Irvin MR; Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA., Kooperberg C; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Minster RL; Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA., Mitchell BD; Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland, Baltimore, MD, USA., Nouraie M; Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., 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., Raffield LM; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Reiner AP; Department of Epidemiology, University of Washington, Seattle, WA, USA., Rich SS; Public Health Science, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., 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., Shoemaker MB; Department of Medicine, Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., 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., 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., Telen MJ; Department of Medicine, Hematology, Duke University Medical Center, Durham, NC, USA., Weiss ST; Department of Medicine, Channing Division of Network Medicine, Harvard Medical School, Boston, MA, USA., Zhang Y; Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Heard-Costa N; Framingham Heart Study, School of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Sun YV; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.; Atlanta VA Health Care System, Decatur, GA, USA., Lin X; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Department of Statistics, Harvard University, Boston, MA, USA., Adrienne Cupples L; Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA., Lange LA; Division of Biomedical Informatics and Personalized Medicine, School of Medicine University of Colorado, Anschutz Medical Campus, Aurora, CO, USA., Liu CT; Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA., 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., North KE; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Justice AE; Population Health Sciences, Geisinger, Danville, PA, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2023 Aug 22. Date of Electronic Publication: 2023 Aug 22.
DOI:	10.1101/2023.08.21.23293271
Abstrakt:	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 ). 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. Competing Interests: 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.
Databáze:	MEDLINE
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