Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.

Autor:	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 of Colorado School of Medicine, Denver, CO 80220, USA., 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 Public Health, Baltimore, MD 21287, USA., 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 Medicine, Winston-Salem, NC 27157, USA., 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., Cushman M; Department of Medicine and Pathology, University of Vermont, College of Medicine, Burlington, VT 05405, USA., Eicher JD; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH, Framingham, MA 01702, USA., Fornage M; Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Franceschini N; Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27514, USA., Fu YP; Cardiovascular Epidemiology and Human Genomics Branch, National Heart, Lung, and Blood Institute, NIH, Framingham, MA 01702, USA., Goodarzi MO; Division of Endocrinology, Diabetes & Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Gottesman O; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Hara K; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Department of Diabetes, Endocrinology, and Metabolism, Tokyo Medical University, Tokyo 163-0023, Japan., Harris TB; Laboratory of Epidemiology and Population Sciences, NIH, Bethesda, MD 20892, USA., Jensen RA; Cardiovascular Health Research Unit, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA., Johnson AD; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH, Framingham, MA 01702, USA., Jhun MA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA., Karter AJ; Division of Research, Kaiser Permanente, Northern California Region, Oakland, CA 94612, USA., Keller MF; Department of Genetics and Pharmacogenomics, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Kho AN; Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Kizer JR; Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10461, USA; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Krauss RM; Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA., Langefeld CD; Center for Public Health Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA., Li X; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA., Liang J; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA., Liu S; Department of Epidemiology, Brown University, Providence, RI 02912, USA; Department of Medicine, Brown University, Providence, RI 02903, USA., Lowe WL Jr; Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Mosley TH; Division of Geriatrics/Gerontology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA., North KE; Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27514, USA., Pacheco JA; Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Peyser PA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA., Patrick AL; Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago., Rice KM; Department of Biostatistics, University of Washington, Seattle, WA 98195, USA., Selvin E; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD 21287, USA; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA., Sims M; Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA., Smith JA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA., Tajuddin SM; Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Baltimore, MD 21224, USA., Vaidya D; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA; GeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA., Wren MP; Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA., Yao J; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA., Zhu X; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA., Ziegler JT; Center for Public Health Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA., Zmuda JM; Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15213, USA., Zonderman AB; Behavioral Epidemiology Section, Laboratory of Epidemiology & Population Science, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, US., Zwinderman AH; Department of Public Health, Academic Medical Center Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands., Adeyemo A; Center for Research on Genomics and Global Health, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA., Boerwinkle E; Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Ferrucci L; Translational Gerontology Branch, National Institute of Aging at Harbor Hospital, Baltimore, MD 21225, USA., Hayes MG; Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Kardia SL; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA., Miljkovic I; Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15213, USA., Pankow JS; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA., Rotimi CN; Center for Research on Genomics and Global Health, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA., Sale MM; Center for Public Health Genomics, Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA., Wagenknecht LE; Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA., Arnett DK; University of Kentucky College of Public Health, Lexington, KY 40563, USA., Chen YD; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA., Nalls MA; Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA., Province MA; Division of Statistical Genomics, Department of Genetics, School of Medicine, Washington University, St Louis, MO 63108, USA., Kao WH; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA., Siscovick DS; Department of Epidemiology, University of Washington, Seattle, WA 98195, USA; Cardiovascular Health Research Unit, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA; The New York Academy of Medicine, New York, NY 10029, USA., Psaty BM; Department of Epidemiology, University of Washington, Seattle, WA 98195, USA; Cardiovascular Health Research Unit, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Health Services, University of Washington, Seattle, WA 98195, USA; Group Health Research Institute, Group Health Cooperative, Seattle, WA 98101, USA., Wilson JG; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA., Loos RJ; 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; The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Dupuis J; Department of Biostatistics, School of Public Health, Boston University, Boston, MA 02118, USA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA., Rich SS; Center for Public Health Genomics, Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA., Florez JC; Diabetes Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA; Programs in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Rotter JI; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA., Morris AP; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Institute of Translational Medicine, Department of Biostatistics, University of Liverpool, Liverpool L69 3BX, UK., Meigs JB; Division of General Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: jmeigs@partners.org.
Jazyk:	angličtina
Zdroj:	American journal of human genetics [Am J Hum Genet] 2016 Jul 07; Vol. 99 (1), pp. 56-75. Date of Electronic Publication: 2016 Jun 16.
DOI:	10.1016/j.ajhg.2016.05.006
Abstrakt:	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. (Copyright © 2016 American Society of Human Genetics. All rights reserved.)
Databáze:	MEDLINE
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