Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
29030599
TITLE
Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.
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.
DATE PUBLISHED
2017 10 13
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2017/05/04
accepted 2017/08/08
entrez 2017/10/15 06:00
pubmed 2017/10/17 06:00
medline 2018/04/07 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Joshi PK Joshi Peter K 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 Pirastu Nicola N Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
Kentistou KA Kentistou Katherine A KA Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, Scotland.
Fischer K Fischer Krista K Estonian Genome Center, University of Tartu, University of Tartu, Tartu, 51010, Estonia.
Hofer E Hofer Edith E Institute of Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, 8036, Austria.
Schraut KE Schraut Katharina E KE Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, Scotland.
Clark DW Clark David W DW Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
Nutile T Nutile Teresa T Institute of Genetics and Biophysics "A. Buzzati-Traverso" - CNR, Naples, 80131, Italy.
Barnes CLK Barnes Catriona L K CLK Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
Timmers PRHJ Timmers Paul R H J PRHJ Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
Shen X Shen Xia X Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
Gandin I Gandin Ilaria I Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, 34137, Italy.
McDaid AF McDaid Aaron F AF Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland.
Hansen TF Hansen Thomas Folkmann TF iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, DK-8000, Denmark.
Gordon SD Gordon Scott D SD QIMR Berghofer Institute of Medical Research, Brisbane, QLD, 4006, Australia.
Giulianini F Giulianini Franco F Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA.
Boutin TS Boutin Thibaud S TS MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
Abdellaoui A Abdellaoui Abdel A Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, Amsterdam Public Health Institute (APH), Amsterdam, 1081BT, Netherlands.
Zhao W Zhao Wei W Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
Medina-Gomez C Medina-Gomez Carolina C Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
Bartz TM Bartz Traci M TM Cardiovascular Health Research Unit, Departments of Biostatistics and Medicine, University of Washington, Seattle, WA, 98101, USA.
Trompet S Trompet Stella S Department of Cardiology, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
Lange LA Lange Leslie A LA Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, 80045, USA.
Raffield L Raffield Laura L Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
van der Spek A van der Spek Ashley A Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
Galesloot TE Galesloot Tessel E TE Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, 6500 HB, The Netherlands.
Proitsi P Proitsi Petroula P MRC Unit for Lifelong Health & Ageing at UCL, University College London, London, WC1B 5JU, UK.
Yanek LR Yanek Lisa R LR Department of Medicine, GeneSTAR Research Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Bielak LF Bielak Lawrence F LF Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
Payton A Payton Antony A Centre for Epidemiology, Division of Population Health, Health Services Research & Primary Care, The University of Manchester, Manchester, Greater, Manchester, M13 9PL, UK.
Murgia F Murgia Federico F Center for Biomedicine, European Academy of Bozen/Bolzano (EURAC), (Affiliated Institute of the University of Lübeck, Lübeck, Germany), Bolzano, 39100, Italy.
Concas MP Concas Maria Pina MP Institute of Genetic and Biomedical Research - Support Unity, National Research Council of Italy, Sassari, 07100, Italy.
Biino G Biino Ginevra G Institute of Molecular Genetics, National Research Council of Italy, Pavia, 27100, Italy.
Tajuddin SM Tajuddin Salman M SM Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore City, MD, 21224, USA.
Seppälä I Seppälä Ilkka I Department of Clinical Chemistry, Fimlab Laboratories and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
Amin N Amin Najaf N Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
Boerwinkle E Boerwinkle Eric E Health Science Center at Houston, UTHealth School of Public Health, University of Texas, Houston, TX, 77030, USA.
Børglum AD Børglum Anders D AD Centre for Integrative Sequencing, iSEQ, Aarhus University, DK-8000, Aarhus C, Denmark.
Campbell A Campbell Archie A Centre for Genomic & Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Demerath EW Demerath Ellen W EW Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, 55454, USA.
Demuth I Demuth Ilja I Institute for Medical and Human Genetics, Charité, Universitätsmedizin Berlin, Berlin, 13353, Germany.
Faul JD Faul Jessica D JD Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48014, USA.
Ford I Ford Ian I Robertson Center for biostatistics, University of Glasgow, Glasgow, G12 8QQ, UK.
Gialluisi A Gialluisi Alessandro A IRCCS Neuromed, Pozzilli (IS), 86077, Italy.
Gögele M Gögele Martin M Center for Biomedicine, European Academy of Bozen/Bolzano (EURAC), (Affiliated Institute of the University of Lübeck, Lübeck, Germany), Bolzano, 39100, Italy.
Graff M Graff MariaElisa M Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27514, USA.
Hingorani A Hingorani Aroon A Institute of Cardiovascular Science, University College London, London, WC1E 6BT, UK.
Hottenga JJ Hottenga Jouke-Jan JJ Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, Amsterdam Public Health Institute (APH), Amsterdam, 1081BT, Netherlands.
Hougaard DM Hougaard David M DM Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, 2300, Denmark.
Hurme MA Hurme Mikko A MA Department of Microbiology and Immunology, Fimlab Laboratories and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
Ikram MA Ikram M Arfan MA Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
Jylhä M Jylhä Marja M Gerontology Research Center, Tampere, Finland, Faculty of Social Sciences, University of Tampere, Tampere, 33104, Finland.
Kuh D Kuh Diana D MRC Unit for Lifelong Health & Ageing at UCL, University College London, London, WC1B 5JU, UK.
Ligthart L Ligthart Lannie L Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, Amsterdam Public Health Institute (APH), Amsterdam, 1081BT, Netherlands.
Lill CM Lill Christina M CM Genetic and Molecular Epidemiology Group, Institute of Neurogenetics, University of Lübeck, 23562, Lübeck, Germany.
Lindenberger U Lindenberger Ulman U Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, 14195, Germany.
Lumley T Lumley Thomas T Department of Statistics, University of Auckland, Auckland, 1010, New Zealand.
Mägi R Mägi Reedik R Estonian Genome Center, University of Tartu, University of Tartu, Tartu, 51010, Estonia.
Marques-Vidal P Marques-Vidal Pedro P Department of Medicine, Internal Medicine, Lausanne University Hospital, Lausanne, 1011, Switzerland.
Medland SE Medland Sarah E SE QIMR Berghofer Institute of Medical Research, Brisbane, QLD, 4006, Australia.
Milani L Milani Lili L Estonian Genome Center, University of Tartu, University of Tartu, Tartu, 51010, Estonia.
Nagy R Nagy Reka R MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
Ollier WER Ollier William E R WER Division of Population Health, Health Services Research & Primary Care, School of Health Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, Greater Manchester, M13 9PL, UK.
Peyser PA Peyser Patricia A PA Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
Pramstaller PP Pramstaller Peter P PP Center for Biomedicine, European Academy of Bozen/Bolzano (EURAC), (Affiliated Institute of the University of Lübeck, Lübeck, Germany), Bolzano, 39100, Italy.
Ridker PM Ridker Paul M PM TH Chan School of Public Health, Harvard Medical School, Boston, MA, 02115, USA.
Rivadeneira F Rivadeneira Fernando F Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
Ruggiero D Ruggiero Daniela D Institute of Genetics and Biophysics "A. Buzzati-Traverso" - CNR, Naples, 80131, Italy.
Saba Y Saba Yasaman Y Austrian Stroke Prevention Study, Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, 8010, Austria.
Schmidt R Schmidt Reinhold R Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, 8036, Austria.
Schmidt H Schmidt Helena H Austrian Stroke Prevention Study, Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, 8010, Austria.
Slagboom PE Slagboom P Eline PE Section of Molecular Epidemiology, Department of medical statistics, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
Smith BH Smith Blair H BH Division of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK.
Smith JA Smith Jennifer A JA Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48014, USA.
Sotoodehnia N Sotoodehnia Nona N Cardiovascular Health Research Unit, Division of Cardiology, University of Washington, Seattle, WA, 98101, USA.
Steinhagen-Thiessen E Steinhagen-Thiessen Elisabeth E Charité Research Group on Geriatrics, Charité, Universitätsmedizin Berlin, Berlin, 13347, Germany.
van Rooij FJA van Rooij Frank J A FJA Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
Verbeek AL Verbeek André L AL Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, 6500 HB, The Netherlands.
Vermeulen SH Vermeulen Sita H SH Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, 6500 HB, The Netherlands.
Vollenweider P Vollenweider Peter P Department of Medicine, Internal Medicine, Lausanne University Hospital, Lausanne, 1011, Switzerland.
Wang Y Wang Yunpeng Y NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, 0450, Norway.
Werge T Werge Thomas T iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, DK-8000, Denmark.
Whitfield JB Whitfield John B JB QIMR Berghofer Institute of Medical Research, Brisbane, QLD, 4006, Australia.
Zonderman AB Zonderman Alan B AB Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore City, MD, 21224, USA.
Lehtimäki T Lehtimäki Terho T Department of Clinical Chemistry, Fimlab Laboratories and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
Evans MK Evans Michele K MK Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore City, MD, 21224, USA.
Pirastu M Pirastu Mario M Institute of Genetic and Biomedical Research - Support Unity, National Research Council of Italy, Sassari, 07100, Italy.
Fuchsberger C Fuchsberger Christian C Center for Biomedicine, European Academy of Bozen/Bolzano (EURAC), (Affiliated Institute of the University of Lübeck, Lübeck, Germany), Bolzano, 39100, Italy.
Bertram L Bertram Lars L Neuroepidemiology and Ageing Research Group, School of Public Health, Imperial College, London, W6 8RP, UK.
Pendleton N Pendleton Neil N Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, Greater Manchester, M13 9PL, UK.
Kardia SLR Kardia Sharon L R SLR Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
Ciullo M Ciullo Marina M IRCCS Neuromed, Pozzilli (IS), 86077, Italy.
Becker DM Becker Diane M DM Department of Medicine, GeneSTAR Research Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Wong A Wong Andrew A MRC Unit for Lifelong Health & Ageing at UCL, University College London, London, WC1B 5JU, UK.
Psaty BM Psaty Bruce M BM Kaiser Permanente Washington Health Research Institute, Seattle, WA, 98101, USA.
van Duijn CM van Duijn Cornelia M CM Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
Wilson JG Wilson James G JG Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Jukema JW Jukema J Wouter JW Department of Cardiology, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
Kiemeney L Kiemeney Lambertus L Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, 6500 HB, The Netherlands.
Uitterlinden AG Uitterlinden André G AG Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CN, Netherlands.
Franceschini N Franceschini Nora N Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27514, USA.
North KE North Kari E KE Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27514, USA.
Weir DR Weir David R DR Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48014, USA.
Metspalu A Metspalu Andres A Estonian Genome Center, University of Tartu, University of Tartu, Tartu, 51010, Estonia.
Boomsma DI Boomsma Dorret I DI Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, Amsterdam Public Health Institute (APH), Amsterdam, 1081BT, Netherlands.
Hayward C Hayward Caroline C MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
Chasman D Chasman Daniel D TH Chan School of Public Health, Harvard Medical School, Boston, MA, 02115, USA.
Martin NG Martin Nicholas G NG QIMR Berghofer Institute of Medical Research, Brisbane, QLD, 4006, Australia.
Sattar N Sattar Naveed N BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TD, UK.
Campbell H Campbell Harry H Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
Esko T Esko Tōnu T Program in Medical and Population Genetics, Broad Institute, Broad Institute, Cambridge, MA, 02142, USA.
Kutalik Z Kutalik Zoltán Z Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland.
Wilson JF Wilson James F JF MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
INVESTIGATORS
JOURNAL
VOLUME: 8
ISSUE: 1
TITLE: Nature communications
ISOABBREVIATION: Nat Commun
YEAR: 2017
MONTH: 10
DAY: 13
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2041-1723
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Commun
COUNTRY: England
ISSNLINKING: 2041-1723
NLMUNIQUEID: 101528555
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
MC_PC_14126 Medical Research Council United Kingdom
R01 HL120393 NHLBI NIH HHS United States
G0900753 Medical Research Council United Kingdom
U01 HL120393 NHLBI NIH HHS United States
MC_UU_12019/1 Medical Research Council United Kingdom
MR/K026992/1 Medical Research Council United Kingdom
R01 HL105756 NHLBI NIH HHS United States
MR/K002279/1 Medical Research Council United Kingdom
Wellcome Trust United Kingdom
G0600237 Medical Research Council United Kingdom
MC_QA137853 Medical Research Council United Kingdom
U01 HL130114 NHLBI NIH HHS United States
T32 HL129982 NHLBI NIH HHS United States
MR/N005813/1 Medical Research Council United Kingdom
MC_PC_U127561128 Medical Research Council United Kingdom
UM1 CA182913 NCI NIH HHS United States
G0100594 Medical Research Council United Kingdom
U54 GM115428 NIGMS NIH HHS United States
BB/F022441/1 Biotechnology and Biological Sciences Research Council United Kingdom
G0901461 Medical Research Council United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alleles
Body Mass Index
Coronary Disease etiology
Education etiology
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
HLA-DQ alpha-Chains genetics
HLA-DRB1 Chains genetics
Humans genetics
Insulin Resistance genetics
Life Style genetics
Lipoprotein(a) genetics
Lipoproteins, HDL blood
Longevity genetics
Lung Neoplasms genetics
Obesity genetics
Polymorphism, Single Nucleotide genetics
Smoking adverse effects
Socioeconomic Factors adverse effects
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 HLA-DQ alpha-Chains
0 HLA-DQA1 antigen
0 HLA-DRB1 Chains
0 Lipoprotein(a)
0 Lipoproteins, HDL
OTHER ID's
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