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Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology.
Spracklen, Cassandra N; Karaderi, Tugce; Yaghootkar, Hanieh; Schurmann, Claudia; Fine, Rebecca S; Kutalik, Zoltan; Preuss, Michael H; Lu, Yingchang; Wittemans, Laura B L; Adair, Linda S; Allison, Matthew; Amin, Najaf; Auer, Paul L; Bartz, Traci M; Blüher, Matthias; Boehnke, Michael; Borja, Judith B; Bork-Jensen, Jette; Broer, Linda; Chasman, Daniel I; Chen, Yii-Der Ida; Chirstofidou, Paraskevi; Demirkan, Ayse; van Duijn, Cornelia M; Feitosa, Mary F; Garcia, Melissa E; Graff, Mariaelisa; Grallert, Harald; Grarup, Niels; Guo, Xiuqing; Haesser, Jeffrey; Hansen, Torben; Harris, Tamara B; Highland, Heather M; Hong, Jaeyoung; Ikram, M Arfan; Ingelsson, Erik; Jackson, Rebecca; Jousilahti, Pekka; Kähönen, Mika; Kizer, Jorge R; Kovacs, Peter; Kriebel, Jennifer; Laakso, Markku; Lange, Leslie A; Lehtimäki, Terho; Li, Jin; Li-Gao, Ruifang; Lind, Lars; Luan, Jian'an.
Afiliação
  • Spracklen CN; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Karaderi T; The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7FZ, UK; Department of Biological Sciences, Faculty of Arts and Sciences, Eastern Mediterranean University, Famagusta, Cyprus; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, U
  • Yaghootkar H; Genetics of Complex Traits, University of Exeter Medical School, Royal Devon & Exeter Hospital, Exeter EX2 5DW, UK; Research Centre for Optimal Health, School of Life Sciences, University of Westminster, London, UK.
  • Schurmann C; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Fine RS; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Kutalik Z; Genetics of Complex Traits, University of Exeter Medical School, Royal Devon & Exeter Hospital, Exeter EX2 5DW, UK; University Center for Primary Care and Public Health, University of Lausanne, Lausanne 1010, Switzerland; Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
  • Preuss MH; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Lu Y; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37203
  • Wittemans LBL; The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7FZ, UK; MRC Epidemiology Unit, University of Cambridge, Cambridge CB2 0QQ, UK.
  • Adair LS; Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA.
  • Allison M; Department of Family Medicine and Public Health, University of California, San Diego, CA 92093, USA.
  • Amin N; Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3015CN, the Netherlands.
  • Auer PL; Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA.
  • Bartz TM; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA; Department of Biostatistics, University of Washington, Seattle, WA 98101, USA.
  • Blüher M; Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig, Leipzig 4103, Germany.
  • Boehnke M; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Borja JB; Office of Population Studies Foundation, Inc, Cebu City, Philippines; Department of Nutrition and Dietetics, University of San Carlos, Cebu City, Philippines.
  • Bork-Jensen J; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
  • Broer L; Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam 3000 CA, the Netherlands.
  • Chasman DI; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Chen YI; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
  • Chirstofidou P; Department of Twin Research and Genetic Epidemiology, Kings College London, London SE1 7EH, UK.
  • Demirkan A; Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3015CN, the Netherlands.
  • van Duijn CM; Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3015CN, the Netherlands.
  • Feitosa MF; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Garcia ME; National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
  • Graff M; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Carolina Center for Genome Sciences, Chapel Hill, NC 27599, USA.
  • Grallert H; Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, München-Neuherberg 85764, Germany; German Center for Diabetes Research, München-Neuherberg 85765, Germany.
  • Grarup N; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
  • Guo X; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
  • Haesser J; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Hansen T; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
  • Harris TB; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
  • Highland HM; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Hong J; Department of Biostatistics, Boston University School of Public Health, Boston, MA 2118, USA.
  • Ikram MA; Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam 3000 CA, the Netherlands; Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam 3000 CA, the Netherlands.
  • Ingelsson E; Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Palo Alto, CA 94304, USA; Stanford Cardiovascular Institute, Stanford University of Medicine, Palo Alto, CA 94304, USA; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala Un
  • Jackson R; Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus, OH 43210, USA.
  • Jousilahti P; Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki 00271, Finland.
  • Kähönen M; Department of Clinical Physiology, Tampere University Hospital, Tampere 33522, Finland; Department of Clinical Physiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33522, Finland.
  • Kizer JR; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Kovacs P; Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig, Leipzig 4103, Germany.
  • Kriebel J; Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, München-Neuherberg 85764, Germany; German Center for Diabetes Research, München-Neuherberg 85765, Germany.
  • Laakso M; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University of Hospital, Kuopio 70029 KYS, Finland.
  • Lange LA; Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado-Denver, Denver, CO 80045, USA.
  • Lehtimäki T; Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33522, Finland.
  • Li J; Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Palo Alto, CA 94304, USA.
  • Li-Gao R; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
  • Lind L; Department of Medical Sciences, Uppsala University, Uppsala 75185, Sweden.
  • Luan J; MRC Epidemiology Unit, University of Cambridge, Cambridge CB2 0QQ, UK.
Am J Hum Genet ; 105(1): 15-28, 2019 07 03.
Article em En | MEDLINE | ID: mdl-31178129
Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tecido Adiposo / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Adiponectina / Exoma / Lipídeos / Obesidade Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Hum Genet Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tecido Adiposo / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Adiponectina / Exoma / Lipídeos / Obesidade Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Hum Genet Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos