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Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.
Joshi, Peter K; Pirastu, Nicola; Kentistou, Katherine A; Fischer, Krista; Hofer, Edith; Schraut, Katharina E; Clark, David W; Nutile, Teresa; Barnes, Catriona L K; Timmers, Paul R H J; Shen, Xia; Gandin, Ilaria; McDaid, Aaron F; Hansen, Thomas Folkmann; Gordon, Scott D; Giulianini, Franco; Boutin, Thibaud S; Abdellaoui, Abdel; Zhao, Wei; Medina-Gomez, Carolina; Bartz, Traci M; Trompet, Stella; Lange, Leslie A; Raffield, Laura; van der Spek, Ashley; Galesloot, Tessel E; Proitsi, Petroula; Yanek, Lisa R; Bielak, Lawrence F; Payton, Antony; Murgia, Federico; Concas, Maria Pina; Biino, Ginevra; Tajuddin, Salman M; Seppälä, Ilkka; Amin, Najaf; Boerwinkle, Eric; Børglum, Anders D; Campbell, Archie; Demerath, Ellen W; Demuth, Ilja; Faul, Jessica D; Ford, Ian; Gialluisi, Alessandro; Gögele, Martin; Graff, MariaElisa; Hingorani, Aroon; Hottenga, Jouke-Jan; Hougaard, David M; Hurme, Mikko A.
Afiliação
  • Joshi PK; Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK. peter.joshi@ed.ac.uk.
  • Pirastu N; Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
  • Kentistou KA; Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
  • Fischer K; Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, Scotland.
  • Hofer E; Estonian Genome Center, University of Tartu, University of Tartu, Tartu, 51010, Estonia.
  • Schraut KE; Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, 8036, Austria.
  • Clark DW; Institute of Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, 8036, Austria.
  • Nutile T; Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
  • Barnes CLK; Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, Scotland.
  • Timmers PRHJ; Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
  • Shen X; Institute of Genetics and Biophysics "A. Buzzati-Traverso" - CNR, Naples, 80131, Italy.
  • Gandin I; Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
  • McDaid AF; Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
  • Hansen TF; Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
  • Gordon SD; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
  • Giulianini F; Department of Medical Sciences, University of Trieste, Trieste, 34100, Italy.
  • Boutin TS; Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, 34137, Italy.
  • Abdellaoui A; Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, 1010, Switzerland.
  • Zhao W; Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland.
  • Medina-Gomez C; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen, Roskilde, DK-4000, Denmark.
  • Bartz TM; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, DK-8000, Denmark.
  • Trompet S; QIMR Berghofer Institute of Medical Research, Brisbane, QLD, 4006, Australia.
  • Lange LA; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA.
  • Raffield L; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
  • van der Spek A; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, Amsterdam Public Health Institute (APH), Amsterdam, 1081BT, Netherlands.
  • Galesloot TE; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Proitsi P; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
  • Yanek LR; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
  • Bielak LF; Cardiovascular Health Research Unit, Departments of Biostatistics and Medicine, University of Washington, Seattle, WA, 98101, USA.
  • Payton A; Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
  • Murgia F; Department of Cardiology, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
  • Concas MP; Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, 80045, USA.
  • Biino G; Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
  • Tajuddin SM; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
  • Seppälä I; Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, 6500 HB, The Netherlands.
  • Amin N; MRC Unit for Lifelong Health & Ageing at UCL, University College London, London, WC1B 5JU, UK.
  • Boerwinkle E; Department of Medicine, GeneSTAR Research Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
  • Børglum AD; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Campbell A; Centre for Epidemiology, Division of Population Health, Health Services Research & Primary Care, The University of Manchester, Manchester, Greater, Manchester, M13 9PL, UK.
  • Demerath EW; Center for Biomedicine, European Academy of Bozen/Bolzano (EURAC), (Affiliated Institute of the University of Lübeck, Lübeck, Germany), Bolzano, 39100, Italy.
  • Demuth I; Institute of Genetic and Biomedical Research - Support Unity, National Research Council of Italy, Sassari, 07100, Italy.
  • Faul JD; Institute of Molecular Genetics, National Research Council of Italy, Pavia, 27100, Italy.
  • Ford I; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore City, MD, 21224, USA.
  • Gialluisi A; Department of Clinical Chemistry, Fimlab Laboratories and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
  • Gögele M; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
  • Graff M; Health Science Center at Houston, UTHealth School of Public Health, University of Texas, Houston, TX, 77030, USA.
  • Hingorani A; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, DK-8000, Denmark.
  • Hottenga JJ; Department of Biomedicine-Human Genetics, Aarhus University, DK-8000, Aarhus C, Denmark.
  • Hougaard DM; Centre for Integrative Sequencing, iSEQ, Aarhus University, DK-8000, Aarhus C, Denmark.
  • Hurme MA; Centre for Genomic & Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Nat Commun ; 8(1): 910, 2017 10 13.
Article em En | MEDLINE | ID: mdl-29030599
ABSTRACT
Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.
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Texto completo: 1 Temas: ECOS / Equidade_desigualdade Bases de dados: MEDLINE Assunto principal: Lipoproteína(a) / Cadeias alfa de HLA-DQ / Cadeias HLA-DRB1 / Estilo de Vida / Longevidade Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Aspecto: Equity_inequality Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
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Texto completo: 1 Temas: ECOS / Equidade_desigualdade Bases de dados: MEDLINE Assunto principal: Lipoproteína(a) / Cadeias alfa de HLA-DQ / Cadeias HLA-DRB1 / Estilo de Vida / Longevidade Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Aspecto: Equity_inequality Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Reino Unido