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

Authors:
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 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 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 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 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 James F Wilson

Nat Commun 2017 10 13;8(1):910. Epub 2017 Oct 13.

Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.

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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http://dx.doi.org/10.1038/s41467-017-00934-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715013PMC
October 2017
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