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Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals.
Nead, Kevin T; Li, Aihua; Wehner, Mackenzie R; Neupane, Binod; Gustafsson, Stefan; Butterworth, Adam; Engert, James C; Davis, A Darlene; Hegele, Robert A; Miller, Ruby; den Hoed, Marcel; Khaw, Kay-Tee; Kilpeläinen, Tuomas O; Wareham, Nick; Edwards, Todd L; Hallmans, Göran; Varga, Tibor V; Kardia, Sharon L R; Smith, Jennifer A; Zhao, Wei; Faul, Jessica D; Weir, David; Mi, Jie; Xi, Bo; Quinteros, Samuel Canizales; Cooper, Cyrus; Sayer, Avan Aihie; Jameson, Karen; Grøntved, Anders; Fornage, Myriam; Sidney, Stephen; Hanis, Craig L; Highland, Heather M; Häring, Hans-Ulrich; Heni, Martin; Lasky-Su, Jessica; Weiss, Scott T; Gerhard, Glenn S; Still, Christopher; Melka, Melkaey M; Pausova, Zdenka; Paus, Tomás; Grant, Struan F A; Hakonarson, Hakon; Price, R Arlen; Wang, Kai; Scherag, Andre; Hebebrand, Johannes; Hinney, Anke; Franks, Paul W.
Afiliação
  • Nead KT; Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
  • Li A; Department of Clinical Epidemiology and Biostatistics.
  • Wehner MR; Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
  • Neupane B; Department of Clinical Epidemiology and Biostatistics.
  • Gustafsson S; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Butterworth A; Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • Engert JC; Population Health Research Institute, McMaster University, and Hamilton Health Sciences, Hamilton General Hospital, Hamilton, ON, Canada L8L 2X.
  • Davis AD; Department of Medicine.
  • Hegele RA; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada L8S 4L8, Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala SE 751 05, Sweden.
  • Miller R; Department of Medicine.
  • den Hoed M; The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada H3H 2R9, Six Nations Health Services, Ohsweken, Canada N0A 1M0.
  • Khaw KT; Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • Kilpeläinen TO; The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada H3H 2R9, Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, London, ON, Canada N6A 5K8.
  • Wareham N; The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada H3H 2R9.
  • Edwards TL; Department of Medicine, University of Western Ontario, London, ON, Canada N6A 3K7.
  • Hallmans G; MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
  • Varga TV; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • Kardia SL; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Copenhagen 2100, Denmark.
  • Smith JA; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Copenhagen 2100, Denmark.
  • Zhao W; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Copenhagen 2100, Denmark.
  • Faul JD; Center for Human Genetics Research, Vanderbilt Epidemiology Center, Department of Medicine, Vanderbilt University, Nashville, TN 37235, USA.
  • Weir D; Center for Human Genetics Research, Vanderbilt Epidemiology Center, Department of Medicine, Vanderbilt University, Nashville, TN 37235, USA.
  • Mi J; Department of Public Health and Clinical Medicine, Umeå University, Umeå 901 87, Sweden.
  • Xi B; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö 205 02, Sweden.
  • Quinteros SC; Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Cooper C; Institute for Social Research, University of Michigan, Ann Arbor, MI 48104, USA, Department of Epidemiology, Capital Institute of Pediatrics, Beijing 100020, China, Department of Maternal and Child Health Care, School of Public Health, Shandong University, Jinan 250100, China.
  • Sayer AA; Institute for Social Research, University of Michigan, Ann Arbor, MI 48104, USA.
  • Jameson K; Institute for Social Research, University of Michigan, Ann Arbor, MI 48104, USA.
  • Grøntved A; Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
  • Fornage M; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Sidney S; National Institute for Health Research Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Hanis CL; National Institute for Health Research Biomedical Research Unit, University of Oxford, Oxford OX3 7LE, UK.
  • Highland HM; National Institute for Health Research Biomedical Research Unit, University of Oxford, Oxford OX3 7LE, UK.
  • Häring HU; Department of Sport Science and Clinical Biomechanics, University of Southern Denmark, Odense DK-5230, Denmark, University of Texas Health Science Center at Houston Institute of Molecular Medicine and Division of Epidemiology Human Genetics and Environmental Sciences, School of Public Health, Housto
  • Heni M; Department of Sport Science and Clinical Biomechanics, University of Southern Denmark, Odense DK-5230, Denmark, University of Texas Health Science Center at Houston Institute of Molecular Medicine and Division of Epidemiology Human Genetics and Environmental Sciences, School of Public Health, Housto
  • Lasky-Su J; Division of Research, Kaiser Permanente of Northern California, Oakland, CA 94612, USA, The Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Weiss ST; Division of Research, Kaiser Permanente of Northern California, Oakland, CA 94612, USA, The Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Gerhard GS; Internal Medicine IV (Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry), University Hospital of Tuebingen, Tübingen 72076, Germany.
  • Still C; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
  • Melka MM; The Department of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Pausova Z; The Department of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Paus T; Center for Genomic Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Grant SF; Department of Biochemistry and Molecular Biology, Institute for Personalized Medicine, Department of Pathology and Laboratory Medicine, Pennsylvania State University, Hershey, PA 17033, USA, Geisinger Obesity Institute, Danville, PA 17822, USA.
  • Hakonarson H; Department of Biochemistry and Molecular Biology, Institute for Personalized Medicine, Department of Pathology and Laboratory Medicine, Pennsylvania State University, Hershey, PA 17033, USA, Geisinger Obesity Institute, Danville, PA 17822, USA.
  • Price RA; The Hospital for Sick Children, Department of Physiology, University of Toronto, Toronto, ON, Canada M5G 1X.
  • Wang K; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK, Rotman Research Institute, University of Toronto, Toronto, Canada M6A 2E1.
  • Scherag A; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Hebebrand J; Department of Pediatrics and.
  • Hinney A; Department of Pediatrics and.
  • Franks PW; Department of Medicine, University of Western Ontario, London, ON, Canada N6A 3K7, MRC Epidemiology Unit, University of Cambridge, Cambridge, UK, Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hum Mol Genet ; 24(12): 3582-94, 2015 Jun 15.
Article em En | MEDLINE | ID: mdl-25784503
ABSTRACT
Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) ≥ 40 kg/m(2)], but their contribution to common obesity (BMI ≥ 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 × 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 × 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (ß = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (ß = 0.02, 95% CI 0.00-0.03; P = 5.57 × 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Variação Genética / Índice de Massa Corporal / Predisposição Genética para Doença / Pró-Proteína Convertase 1 / Obesidade Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Variação Genética / Índice de Massa Corporal / Predisposição Genética para Doença / Pró-Proteína Convertase 1 / Obesidade Idioma: En Ano de publicação: 2015 Tipo de documento: Article