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Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.
Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa; Kabagambe, Edmond Kato; Hong, Jaeyoung; Ng, Maggie C Y; Hivert, Marie-France; Lu, Yingchang; An, Ping; Bentley, Amy R; Drolet, Anne M; Gaulton, Kyle J; Guo, Xiuqing; Armstrong, Loren L; Irvin, Marguerite R; Li, Man; Lipovich, Leonard; Rybin, Denis V; Taylor, Kent D; Agyemang, Charles; Palmer, Nicholette D; Cade, Brian E; Chen, Wei-Min; Dauriz, Marco; Delaney, Joseph A C; Edwards, Todd L; Evans, Daniel S; Evans, Michele K; Lange, Leslie A; Leong, Aaron; Liu, Jingmin; Liu, Yongmei; Nayak, Uma; Patel, Sanjay R; Porneala, Bianca C; Rasmussen-Torvik, Laura J; Snijder, Marieke B; Stallings, Sarah C; Tanaka, Toshiko; Yanek, Lisa R; Zhao, Wei; Becker, Diane M; Bielak, Lawrence F; Biggs, Mary L; Bottinger, Erwin P; Bowden, Donald W; Chen, Guanjie; Correa, Adolfo; Couper, David J; Crawford, Dana C.
Afiliação
  • Liu CT; Department of Biostatistics, School of Public Health, Boston University, Boston, MA 02118, USA. Electronic address: ctliu@bu.edu.
  • Raghavan S; Division of General Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Veterans Affairs Medical Center, Eastern Colorado Health Care System, Denver, CO 80220, USA; Division of General Internal Medicine, Department of Medicine, University o
  • Maruthur N; Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD 21287, USA; Department of Epidemiology, Johns Hopkins University Bloomberg School of
  • Kabagambe EK; Division of Epidemiology, Department of Medicine, School of Medicine, Vanderbilt University Medical Center, Nashville, TN 37203, USA.
  • Hong J; Department of Biostatistics, School of Public Health, Boston University, Boston, MA 02118, USA.
  • Ng MC; Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Center for Diabetes Research, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
  • Hivert MF; Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA 02215, USA; Diabetes Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Universite de Sherbrooke, Sherbrooke, QC J1G 0A2, Canada.
  • Lu Y; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • An P; Division of Statistical Genomics, Department of Genetics, School of Medicine, Washington University, St Louis, MO 63108, USA.
  • Bentley AR; Center for Research on Genomics and Global Health, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Drolet AM; Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
  • Gaulton KJ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Guo X; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
  • Armstrong LL; Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
  • Irvin MR; Department of Epidemiology, School of Public Health, University of Alabama - Birmingham, Birmingham, AL 35294, USA.
  • Li M; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
  • Lipovich L; Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48201, USA; Department of Neurology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
  • Rybin DV; Department of Biostatistics, School of Public Health, Boston University, Boston, MA 02118, USA.
  • Taylor KD; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
  • Agyemang C; Department of Public Health, Academic Medical Center Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands.
  • Palmer ND; Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
  • Cade BE; Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Chen WM; Center for Public Health Genomics, Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
  • Dauriz M; Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of Verona, 37126 Verona, Italy.
  • Delaney JA; Department of Epidemiology, University of Washington, Seattle, WA 98195, USA.
  • Edwards TL; Division of Epidemiology, Department of Medicine, School of Medicine, Vanderbilt University Medical Center, Nashville, TN 37203, USA.
  • Evans DS; California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
  • Evans MK; Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Lange LA; Department of Genetics, University of North Carolina, Chapel Hill, NC 27607, USA.
  • Leong A; Division of General Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Liu J; Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Liu Y; Center for Human Genetics, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
  • Nayak U; Center for Public Health Genomics, Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
  • Patel SR; Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Porneala BC; Division of General Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Rasmussen-Torvik LJ; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
  • Snijder MB; Department of Public Health, Academic Medical Center Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands.
  • Stallings SC; Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN 37203, USA.
  • Tanaka T; Translational Gerontology Branch, National Institute of Aging at Harbor Hospital, Baltimore, MD 21225, USA.
  • Yanek LR; GeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
  • Zhao W; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
  • Becker DM; GeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA; Department of Health Policy and Management, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
  • Bielak LF; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
  • Biggs ML; Department of Biostatistics, University of Washington, Seattle, WA 98195, USA; Cardiovascular Health Research Unit, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA.
  • Bottinger EP; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Bowden DW; Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Center for Diabetes Research, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Department of Biochemistry, Wake Forest University School of Medicin
  • Chen G; Center for Research on Genomics and Global Health, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Correa A; Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Couper DJ; Collaborative Studies Coordinating Center, Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27514, USA.
  • Crawford DC; Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
Am J Hum Genet ; 99(1): 56-75, 2016 Jul 07.
Article em En | MEDLINE | ID: mdl-27321945
ABSTRACT
Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glicemia / Etnicidade / Jejum / Grupos Raciais / Diabetes Mellitus Tipo 2 / Insulina Tipo de estudo: Prognostic_studies / Systematic_reviews Limite: Female / Humans / Male Idioma: En Revista: Am J Hum Genet Ano de publicação: 2016 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glicemia / Etnicidade / Jejum / Grupos Raciais / Diabetes Mellitus Tipo 2 / Insulina Tipo de estudo: Prognostic_studies / Systematic_reviews Limite: Female / Humans / Male Idioma: En Revista: Am J Hum Genet Ano de publicação: 2016 Tipo de documento: Article