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WHOLE GENOME SEQUENCING ANALYSIS OF BODY MASS INDEX IDENTIFIES NOVEL AFRICAN ANCESTRY-SPECIFIC RISK ALLELE.
Zhang, Xinruo; Brody, Jennifer A; Graff, Mariaelisa; Highland, Heather M; Chami, Nathalie; Xu, Hanfei; Wang, Zhe; Ferrier, Kendra; Chittoor, Geetha; Josyula, Navya S; 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; Chuang, Lee-Ming; Conomos, Matthew P; DeMeo, Dawn L; Du, Margaret; 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.
Affiliation
  • 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.
  • Buth EJ; Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA, USA.
  • Carlson CS; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Chang KM; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Chavan S; The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
  • Chiu YF; University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Chuang LM; Department of Medicine, School of Medicine, University of Colorado, Aurora, CO, USA.
  • Conomos MP; Institute of Population Health Sciences, National Health Research Institutes, Taipei, Taiwan.
  • DeMeo DL; Department of Internal Medicine, Division of Metabolism/Endocrinology, National Taiwan University Hospital, Taipei, Taiwan.
  • Du M; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Duggirala R; Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Eng C; Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Fohner AE; Life Sciences, College of Arts and Sciences, Texas A&M University-San Antonio, San Antonio, TX, USA.
  • Freedman BI; Department of Medicine, Lung Biology Center, University of California, San Francisco, San Francisco, CA, USA.
  • Garrett ME; Epidemiology, Institute of Public Health Genetics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Guo X; Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Haiman C; Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
  • Heavner BD; 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.
  • Hidalgo B; Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Hixson JE; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Ho YL; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA.
  • Hobbs BD; Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Hu D; Veterans Affairs Boston Healthcare System, Boston, MA, USA.
  • Hui Q; Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Hwu CM; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Jackson RD; Department of Medicine, Lung Biology Center, University of California, San Francisco, San Francisco, CA, USA.
  • Jain D; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
  • Kalyani RR; Atlanta VA Health Care System, Decatur, GA, USA.
  • Kardia SLR; Department of Medicine, Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan, Taiwan.
  • Kelly TN; Endocrinology, Ohio State University, Columbus, OH, USA.
  • Lange EM; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • LeNoir M; Department of Medicine, Endocrinology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
medRxiv ; 2023 Aug 22.
Article in En | MEDLINE | ID: mdl-37662265
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). 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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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Etiology_studies / Risk_factors_studies Language: En Journal: MedRxiv Year: 2023 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Etiology_studies / Risk_factors_studies Language: En Journal: MedRxiv Year: 2023 Type: Article Affiliation country: United States