Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity

Peter K. Joshi (), Nicola Pirastu, Katherine A. Kentistou, Krista Fischer, Edith Hofer, Katharina E. Schraut, David W. Clark, Teresa Nutile, Catriona L. K. Barnes, Paul R. H. J. Timmers, Xia Shen, Ilaria Gandin, Aaron F. McDaid, Thomas Folkmann Hansen, Scott D. Gordon, Franco Giulianini, Thibaud S. Boutin, Abdel Abdellaoui, Wei Zhao, Carolina Medina-Gomez, Traci M. Bartz, Stella Trompet, Leslie A. Lange, Laura Raffield, Ashley Spek, Tessel E. Galesloot, Petroula Proitsi, Lisa R. Yanek, Lawrence F. Bielak, Antony Payton, Federico Murgia, Maria Pina Concas, Ginevra Biino, Salman M. Tajuddin, Ilkka Seppälä, Najaf Amin, Eric Boerwinkle, Anders D. Børglum, Archie Campbell, Ellen W. Demerath, Ilja Demuth, Jessica D. Faul, Ian Ford, Alessandro Gialluisi, Martin Gögele, MariaElisa Graff, Aroon Hingorani, Jouke-Jan Hottenga, David M. Hougaard, Mikko A. Hurme, M. Arfan Ikram, Marja Jylhä, Diana Kuh, Lannie Ligthart, Christina M. Lill, Ulman Lindenberger, Thomas Lumley, Reedik Mägi, Pedro Marques-Vidal, Sarah E. Medland, Lili Milani, Reka Nagy, William E. R. Ollier, Patricia A. Peyser, Peter P. Pramstaller, Paul M. Ridker, Fernando Rivadeneira, Daniela Ruggiero, Yasaman Saba, Reinhold Schmidt, Helena Schmidt, P. Eline Slagboom, Blair H. Smith, Jennifer A. Smith, Nona Sotoodehnia, Elisabeth Steinhagen-Thiessen, Frank J. A. Rooij, André L. Verbeek, Sita H. Vermeulen, Peter Vollenweider, Yunpeng Wang, Thomas Werge, John B. Whitfield, Alan B. Zonderman, Terho Lehtimäki, Michele K. Evans, Mario Pirastu, Christian Fuchsberger, Lars Bertram, Neil Pendleton, Sharon L. R. Kardia, Marina Ciullo, Diane M. Becker, Andrew Wong, Bruce M. Psaty, Cornelia M. Duijn, James G. Wilson, J. Wouter Jukema, Lambertus Kiemeney, André G. Uitterlinden, Nora Franceschini, Kari E. North, David R. Weir, Andres Metspalu, Dorret I. Boomsma, Caroline Hayward, Daniel Chasman, Nicholas G. Martin, Naveed Sattar, Harry Campbell, Tōnu Esko, Zoltán Kutalik and James F. Wilson
Additional contact information
Peter K. Joshi: University of Edinburgh
Nicola Pirastu: University of Edinburgh
Katherine A. Kentistou: University of Edinburgh
Krista Fischer: University of Tartu, University of Tartu
Edith Hofer: Medical University of Graz
Katharina E. Schraut: University of Edinburgh
David W. Clark: University of Edinburgh
Teresa Nutile: Institute of Genetics and Biophysics “A. Buzzati-Traverso” - CNR
Catriona L. K. Barnes: University of Edinburgh
Paul R. H. J. Timmers: University of Edinburgh
Xia Shen: University of Edinburgh
Ilaria Gandin: University of Trieste
Aaron F. McDaid: Lausanne University Hospital
Thomas Folkmann Hansen: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen
Scott D. Gordon: QIMR Berghofer Institute of Medical Research
Franco Giulianini: Brigham and Women’s Hospital
Thibaud S. Boutin: University of Edinburgh, Western General Hospital
Abdel Abdellaoui: Vrije Universiteit, Amsterdam, Amsterdam Public Health Institute (APH)
Wei Zhao: University of Michigan
Carolina Medina-Gomez: Erasmus University Medical Center
Traci M. Bartz: University of Washington
Stella Trompet: Leiden University Medical Center
Leslie A. Lange: University of Colorado Denver, Anschutz Medical Campus
Laura Raffield: University of North Carolina
Ashley Spek: Erasmus University Medical Center
Tessel E. Galesloot: Radboud university medical center
Petroula Proitsi: University College London
Lisa R. Yanek: Johns Hopkins University School of Medicine
Lawrence F. Bielak: University of Michigan
Antony Payton: The University of Manchester
Federico Murgia: (Affiliated Institute of the University of Lübeck, Lübeck, Germany)
Maria Pina Concas: National Research Council of Italy
Ginevra Biino: National Research Council of Italy
Salman M. Tajuddin: National Institutes of Health
Ilkka Seppälä: University of Tampere
Najaf Amin: Erasmus University Medical Center
Eric Boerwinkle: University of Texas
Anders D. Børglum: The Lundbeck Foundation Initiative for Integrative Psychiatric Research
Archie Campbell: University of Edinburgh
Ellen W. Demerath: University of Minnesota
Ilja Demuth: Universitätsmedizin Berlin
Jessica D. Faul: University of Michigan
Ian Ford: University of Glasgow
Alessandro Gialluisi: IRCCS Neuromed
Martin Gögele: (Affiliated Institute of the University of Lübeck, Lübeck, Germany)
MariaElisa Graff: University of North Carolina
Aroon Hingorani: University College London
Jouke-Jan Hottenga: Vrije Universiteit, Amsterdam, Amsterdam Public Health Institute (APH)
David M. Hougaard: The Lundbeck Foundation Initiative for Integrative Psychiatric Research
Mikko A. Hurme: University of Tampere
M. Arfan Ikram: Erasmus University Medical Center
Marja Jylhä: University of Tampere
Diana Kuh: University College London
Lannie Ligthart: Vrije Universiteit, Amsterdam, Amsterdam Public Health Institute (APH)
Christina M. Lill: University of Lübeck
Ulman Lindenberger: Center for Lifespan Psychology, Max Planck Institute for Human Development
Thomas Lumley: University of Auckland
Reedik Mägi: University of Tartu, University of Tartu
Pedro Marques-Vidal: Lausanne University Hospital
Sarah E. Medland: QIMR Berghofer Institute of Medical Research
Lili Milani: University of Tartu, University of Tartu
Reka Nagy: University of Edinburgh, Western General Hospital
William E. R. Ollier: University of Manchester
Patricia A. Peyser: University of Michigan
Peter P. Pramstaller: (Affiliated Institute of the University of Lübeck, Lübeck, Germany)
Paul M. Ridker: Brigham and Women’s Hospital
Fernando Rivadeneira: Erasmus University Medical Center
Daniela Ruggiero: Institute of Genetics and Biophysics “A. Buzzati-Traverso” - CNR
Yasaman Saba: Medical University of Graz
Reinhold Schmidt: Medical University of Graz
Helena Schmidt: Medical University of Graz
P. Eline Slagboom: Leiden University Medical Center
Blair H. Smith: University of Dundee
Jennifer A. Smith: University of Michigan
Nona Sotoodehnia: University of Washington
Elisabeth Steinhagen-Thiessen: Universitätsmedizin Berlin
Frank J. A. Rooij: Erasmus University Medical Center
André L. Verbeek: Radboud university medical center
Sita H. Vermeulen: Radboud university medical center
Peter Vollenweider: Lausanne University Hospital
Yunpeng Wang: The Lundbeck Foundation Initiative for Integrative Psychiatric Research
Thomas Werge: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen
John B. Whitfield: QIMR Berghofer Institute of Medical Research
Alan B. Zonderman: National Institutes of Health
Terho Lehtimäki: University of Tampere
Michele K. Evans: National Institutes of Health
Mario Pirastu: National Research Council of Italy
Christian Fuchsberger: (Affiliated Institute of the University of Lübeck, Lübeck, Germany)
Lars Bertram: University of Lübeck
Neil Pendleton: University of Manchester
Sharon L. R. Kardia: University of Michigan
Marina Ciullo: Institute of Genetics and Biophysics “A. Buzzati-Traverso” - CNR
Diane M. Becker: Johns Hopkins University School of Medicine
Andrew Wong: University College London
Bruce M. Psaty: University of Washington
Cornelia M. Duijn: Erasmus University Medical Center
James G. Wilson: University of Mississippi Medical Center
J. Wouter Jukema: Leiden University Medical Center
Lambertus Kiemeney: Radboud university medical center
André G. Uitterlinden: Erasmus University Medical Center
Nora Franceschini: University of North Carolina
Kari E. North: University of North Carolina
David R. Weir: University of Michigan
Andres Metspalu: University of Tartu, University of Tartu
Dorret I. Boomsma: Vrije Universiteit, Amsterdam, Amsterdam Public Health Institute (APH)
Caroline Hayward: University of Edinburgh, Western General Hospital
Daniel Chasman: Brigham and Women’s Hospital
Nicholas G. Martin: QIMR Berghofer Institute of Medical Research
Naveed Sattar: University of Glasgow
Harry Campbell: University of Edinburgh
Tōnu Esko: University of Tartu, University of Tartu
Zoltán Kutalik: Lausanne University Hospital
James F. Wilson: University of Edinburgh

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00934-5

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