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-GomezTraci M. Bartz, Stella Trompet, Leslie A. Lange, Laura Raffield, Ashley van der 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 D. 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 Paul 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. van 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. van Duijn, James G. Wilson, J. Wouter Jukema, Lambertus A. Kiemeney, André G. Uitterlinden, Nora Franceschini, Kari E. North, David R. Weir, Andres Metspalu, Dorret I. Boomsma, Caroline Hayward, Daniel I. Chasman, Nicholas G. Martin, Naveed Sattar, Harry Campbell, Tōnu Esko, Zoltán Kutalik, James F. Wilson

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    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.
    Original languageEnglish
    Article number910
    Pages (from-to)1-13
    Number of pages13
    JournalNature Communications
    Volume8
    DOIs
    Publication statusPublished - 13 Oct 2017

    Keywords

    • Genetics research
    • Genome-wide association studies
    • Quantitative trait

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  • Cite this

    Joshi, P. K., Pirastu, N., Kentistou, K. A., Fischer, K., Hofer, E., Schraut, K. E., Clark, D. W., Nutile, T., Barnes, C. L. K., Timmers, P. R. H. J., Shen, X., Gandin, I., McDaid, A. F., Hansen, T. F., Gordon, S. D., Giulianini, F., Boutin, T. S., Abdellaoui, A., Zhao, W., ... Wilson, J. F. (2017). Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. Nature Communications, 8, 1-13. [910]. https://doi.org/10.1038/s41467-017-00934-5