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CA055075, HL34594, HL088521, U01HG004399, DK080140,"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity Reviews"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Previously, a single nucleotide polymorphism (<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>), rs9939609, in the <jats:styled-content style=\"fixed-case\"><jats:italic>FTO<\/jats:italic><\/jats:styled-content> gene showed a much stronger association with all\u2010cause mortality than expected from its association with body mass index (<jats:styled-content style=\"fixed-case\">BMI<\/jats:styled-content>), body fat mass index (<jats:styled-content style=\"fixed-case\">FMI<\/jats:styled-content>) and waist circumference (<jats:styled-content style=\"fixed-case\">WC<\/jats:styled-content>). This finding implies that the <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content> has strong pleiotropic effects on adiposity and adiposity\u2010independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta\u2010analysis of similar data from 34 longitudinal studies including 169,551 adult <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>aucasians among whom 27,100 died during follow\u2010up. Linear regression showed that the minor allele of the <jats:styled-content style=\"fixed-case\"><jats:italic>FTO<\/jats:italic> SNP<\/jats:styled-content> was associated with greater <jats:styled-content style=\"fixed-case\">BMI<\/jats:styled-content> (<jats:italic>n<\/jats:italic>\u2009=\u2009169,551; 0.32\u2009kg\u2009m<jats:sup>\u22122<\/jats:sup>; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.28\u20130.32, <jats:italic>P<\/jats:italic>\u2009&lt;\u20091\u2009\u00d7\u200910<jats:sup>\u221232<\/jats:sup>), <jats:styled-content style=\"fixed-case\">WC<\/jats:styled-content> (<jats:italic>n<\/jats:italic>\u2009=\u2009152,631; 0.76\u2009cm; 0.68\u20130.84, <jats:italic>P<\/jats:italic>\u2009&lt;\u20091\u2009\u00d7\u200910<jats:sup>\u221232<\/jats:sup>) and <jats:styled-content style=\"fixed-case\">FMI<\/jats:styled-content> (<jats:italic>n<\/jats:italic>\u2009=\u200948,192; 0.17\u2009kg\u2009m<jats:sup>\u22122<\/jats:sup>; 0.13\u20130.22, <jats:italic>P<\/jats:italic>\u2009=\u20091.0\u2009\u00d7\u200910<jats:sup>\u221213<\/jats:sup>). <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>ox proportional hazard regression analyses for mortality showed that the hazards ratio (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>) for the minor allele of the <jats:styled-content style=\"fixed-case\"><jats:italic>FTO<\/jats:italic> SNPs<\/jats:styled-content> was 1.02 (1.00\u20131.04, <jats:italic>P<\/jats:italic>\u2009=\u20090.097), but the apparent excess risk was eliminated after adjustment for <jats:styled-content style=\"fixed-case\">BMI<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">WC<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>: 1.00; 0.98\u20131.03, <jats:italic>P<\/jats:italic>\u2009=\u20090.662) and for <jats:styled-content style=\"fixed-case\">FMI<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>: 1.00; 0.96\u20131.04, <jats:italic>P<\/jats:italic>\u2009=\u20090.932). In conclusion, this study does not support that the <jats:styled-content style=\"fixed-case\"><jats:italic>FTO<\/jats:italic> SNP<\/jats:styled-content> is associated with all\u2010cause mortality independently of the adiposity phenotypes.<\/jats:p>","DOI":"10.1111\/obr.12263","type":"journal-article","created":{"date-parts":[[2015,3,5]],"date-time":"2015-03-05T13:26:47Z","timestamp":1425562007000},"page":"327-340","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Is the adiposity\u2010associated <scp><i>FTO<\/i><\/scp> gene variant related to all\u2010cause mortality independent of adiposity? Meta\u2010analysis of data from 169,551 <scp>C<\/scp>aucasian adults"],"prefix":"10.1111","volume":"16","author":[{"given":"E.","family":"Zimmermann","sequence":"first","affiliation":[{"name":"Institute of Preventive Medicine Bispebjerg and Frederiksberg Hospitals, The Capital Region  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. H.","family":"\u00c4ngquist","sequence":"additional","affiliation":[{"name":"Institute of Preventive Medicine Bispebjerg and Frederiksberg Hospitals, The Capital Region  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. S.","family":"Mirza","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus Medical Centre  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. H.","family":"Zhao","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit Institute of Metabolic Science Addenbrooke's Hospital University of Cambridge  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. I.","family":"Chasman","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine Brigham and Women's Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Estonian Genome Center University of Tartu  Tartu Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Q.","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health Albert Einstein College of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. V.","family":"Smith","sequence":"additional","affiliation":[{"name":"Icelandic Heart Association  Kopavogur Iceland"},{"name":"University of Icelandic  Reykajvik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Thinggaard","sequence":"additional","affiliation":[{"name":"The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Institute of Public Health University of Southern Denmark  Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. N.","family":"Jarczok","sequence":"additional","affiliation":[{"name":"Mannheim Institute of Public Health, Social and Preventive Medicine Medical Faculty Mannheim Heidelberg University  Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. A.","family":"Nalls","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics Intramural Research Program National Institute on Aging  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Trompet","sequence":"additional","affiliation":[{"name":"Department of Cardiology Leiden University Medical Center  Leiden The Netherlands"},{"name":"Department of Gerontology and Geriatrics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. 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P.","family":"Lyytik\u00e4inen","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Fimlab Laboratories  Tampere Finland"},{"name":"School of Medicine University of Tampere  Tampere Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Verweij","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Center Groningen University of Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Mueller\u2010Nurasyid","sequence":"additional","affiliation":[{"name":"Department of Medicine I Ludwig\u2010Maximilians\u2010University  Munich Germany"},{"name":"Institute of Medical Informatics, Biometry and Epidemiology Chair of Genetic Epidemiology Ludwig\u2010Maximilians\u2010Universit\u00e4t  Munich Germany"},{"name":"Institute of Genetic Epidemiology Helmholtz Zentrum M\u00fcnchen \u2013 German Research Center for Environmental Health  Neuherberg Germany"},{"name":"Deutsches Forschungszentrum f\u00fcr Herz\u2010Kreislauferkrankungen (DZHK) Partner site Munich Heart Alliance  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Vikstr\u00f6m","sequence":"additional","affiliation":[{"name":"Karolinska Institutet Institute of Environmental Medicine Unit of Cardiovascular Epidemiology  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Marques\u2010Vidal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Internal Medicine Lausanne University Hospital (CHUV)  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Wong","sequence":"additional","affiliation":[{"name":"MRC Unit for Lifelong Health and Ageing University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Meidtner","sequence":"additional","affiliation":[{"name":"Department of Molecular Epidemiology German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke  Nuthetal Germany"},{"name":"Department of Epidemiology German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke  Nuthetal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. P.","family":"Middelberg","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute  Brisbane Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. J.","family":"Strawbridge","sequence":"additional","affiliation":[{"name":"Atherosclerosis Research Unit Department of Medicine Solna Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Christiansen","sequence":"additional","affiliation":[{"name":"The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Institute of Public Health University of Southern Denmark  Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"The FTO\u2010Mortality Collaborating Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. O.","family":"Kyvik","sequence":"additional","affiliation":[{"name":"Institute of Regional Health Services Research and Odense Patient data Explorative Network Odense University Hospital  Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Hamsten","sequence":"additional","affiliation":[{"name":"Atherosclerosis Research Unit Department of Medicine Solna Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"J\u00e4\u00e4skel\u00e4inen","sequence":"additional","affiliation":[{"name":"Institute of Public Health and Clinical Nutrition University of Eastern Finland  Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Tj\u00f8nneland","sequence":"additional","affiliation":[{"name":"Danish Cancer Society Research Centre  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. G.","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Diabetes Prevention Unit Department of Chronic Disease Prevention National Institute for Health and Welfare  Helsinki Finland"},{"name":"Department of General Practice and Primary Health Care Institute of Clinical Medicine University of Helsinki  Helsinki Finland"},{"name":"Folkh\u00e4lsan Research Centre  Helsinki Finland"},{"name":"Unit of General Practice Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. B.","family":"Whitfield","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute  Brisbane Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Boeing","sequence":"additional","affiliation":[{"name":"Department of Epidemiology German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke  Nuthetal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Hardy","sequence":"additional","affiliation":[{"name":"MRC Unit for Lifelong Health and Ageing University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Vollenweider","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Internal Medicine Lausanne University Hospital (CHUV)  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Leander","sequence":"additional","affiliation":[{"name":"Karolinska Institutet Institute of Environmental Medicine Unit of Cardiovascular Epidemiology  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Peters","sequence":"additional","affiliation":[{"name":"Deutsches Forschungszentrum f\u00fcr Herz\u2010Kreislauferkrankungen (DZHK) Partner site Munich Heart Alliance  Munich Germany"},{"name":"Institute of Epidemiology II Helmholtz Zentrum M\u00fcnchen \u2013 German Research Center for Environmental Health  Neuherberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"van der Harst","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Center Groningen University of Groningen  Groningen The Netherlands"},{"name":"Department of Genetic University Medical Center Groningen University of Groningen  Groningen The Netherlands"},{"name":"Durrer Center for Cardiogenetic Research ICIN\u2010Neterlands Heart Institute  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Kumari","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health University College London  London UK"},{"name":"ISER University of Essex  Colchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Lehtim\u00e4ki","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Fimlab Laboratories  Tampere Finland"},{"name":"School of Medicine University of Tampere  Tampere Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Meirhaeghe","sequence":"additional","affiliation":[{"name":"Inserm U744 Institut Pasteur de Lille University Lille Nord de France  Lille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Tuomilehto","sequence":"additional","affiliation":[{"name":"Diabetes Prevention Unit National Institute for Health and Welfare  Helsinki Finland"},{"name":"Centre for Vascular Prevention Danube\u2010University Krems  Krems Austria"},{"name":"Instituto de Investigacion Sanitaria del Hospital Universario LaPaz (IdiPAZ)  Madrid Spain"},{"name":"Diabetes Research Group King Abdulaziz University  Jeddah Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.\u2010H.","family":"J\u00f6ckel","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Ben\u2010Shlomo","sequence":"additional","affiliation":[{"name":"School of Social and Community Medicine University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Sattar","sequence":"additional","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre Faculty of Medicine  Glasgow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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