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New genetic loci link adipose and insulin biology to body fat distribution.
Shungin, Dmitry; Winkler, Thomas W; Croteau-Chonka, Damien C; Ferreira, Teresa; Locke, Adam E; Mägi, Reedik; Strawbridge, Rona J; Pers, Tune H; Fischer, Krista; Justice, Anne E; Workalemahu, Tsegaselassie; Wu, Joseph M W; Buchkovich, Martin L; Heard-Costa, Nancy L; Roman, Tamara S; Drong, Alexander W; Song, Ci; Gustafsson, Stefan; Day, Felix R; Esko, Tonu; Fall, Tove; Kutalik, Zoltán; Luan, Jian'an; Randall, Joshua C; Scherag, André; Vedantam, Sailaja; Wood, Andrew R; Chen, Jin; Fehrmann, Rudolf; Karjalainen, Juha; Kahali, Bratati; Liu, Ching-Ti; Schmidt, Ellen M; Absher, Devin; Amin, Najaf; Anderson, Denise; Beekman, Marian; Bragg-Gresham, Jennifer L; Buyske, Steven; Demirkan, Ayse; Ehret, Georg B; Feitosa, Mary F; Goel, Anuj; Jackson, Anne U; Johnson, Toby; Kleber, Marcus E; Kristiansson, Kati; Mangino, Massimo; Leach, Irene Mateo; Medina-Gomez, Carolina.
Afiliação
  • Shungin D; Department of Public Health and Clinical Medicine, Unit of Medicine, Umeå University, Umeå 901 87, Sweden.
  • Winkler TW; Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Center, Skåne University Hosptial, Malmö 205 02, Sweden.
  • Croteau-Chonka DC; Department of Odontology, Umeå University, Umeå 901 85, Sweden.
  • Ferreira T; Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, D-93053 Regensburg, Germany.
  • Locke AE; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Mägi R; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Strawbridge RJ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Pers TH; Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Fischer K; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Justice AE; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
  • Workalemahu T; Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
  • Wu JMW; Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA 02115, USA.
  • Buchkovich ML; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge 02142, MA, USA.
  • Heard-Costa NL; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Roman TS; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby 2800, Denmark.
  • Drong AW; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
  • Song C; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Gustafsson S; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
  • Day FR; Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
  • Esko T; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Fall T; National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham MA 01702, USA.
  • Kutalik Z; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA.
  • Luan J; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Randall JC; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Scherag A; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden.
  • Vedantam S; Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden.
  • Wood AR; Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden.
  • Chen J; Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden.
  • Fehrmann R; Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden.
  • Karjalainen J; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Kahali B; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
  • Liu CT; Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA 02115, USA.
  • Schmidt EM; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge 02142, MA, USA.
  • Absher D; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Amin N; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden.
  • Anderson D; Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden.
  • Beekman M; Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden.
  • Bragg-Gresham JL; Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1010, Switzerland.
  • Buyske S; Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
  • Demirkan A; Department of Medical Genetics, University of Lausanne, Lausanne 1005, Switzerland.
  • Ehret GB; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Feitosa MF; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Goel A; Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
  • Jackson AU; Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University Hospital Essen, Essen, Germany.
  • Johnson T; Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.
  • Kleber ME; Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA 02115, USA.
  • Kristiansson K; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge 02142, MA, USA.
  • Mangino M; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK.
  • Leach IM; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Medina-Gomez C; Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
Nature ; 518(7538): 187-196, 2015 Feb 12.
Article em En | MEDLINE | ID: mdl-25673412
ABSTRACT
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tecido Adiposo / Locos de Características Quantitativas / Distribuição da Gordura Corporal / Estudo de Associação Genômica Ampla / Insulina Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tecido Adiposo / Locos de Características Quantitativas / Distribuição da Gordura Corporal / Estudo de Associação Genômica Ampla / Insulina Idioma: En Ano de publicação: 2015 Tipo de documento: Article