Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity
Authors: 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. , Ikram M. Arfan , Jylhä Marja , Kuh Diana , Ligthart Lannie , Lill Christina M. , Lindenberger Ulman , Lumley Thomas , Mägi Reedik , Marques-Vidal Pedro , Medland Sarah E. , Milani Lili , Nagy Reka , Ollier William E. R. , Peyser Patricia A. , Pramstaller Peter P. , Ridker Paul M. , Rivadeneira Fernando , Ruggiero Daniela , Saba Yasaman , Schmidt Reinhold , Schmidt Helena , Slagboom P. Eline , Smith Blair H. , Smith Jennifer A. , Sotoodehnia Nona , Steinhagen-Thiessen Elisabeth , van Rooij Frank J. A. , Verbeek André L. , Vermeulen Sita H. , Vollenweider Peter , Wang Yunpeng , Werge Thomas , Whitfield John B. , Zonderman Alan B. , Lehtimäki Terho , Evans Michele K. , Pirastu Mario , Fuchsberger Christian , Bertram Lars , Pendleton Neil , Kardia Sharon L. R. , Ciullo Marina , Becker Diane M. , Wong Andrew , Psaty Bruce M. , van Duijn Cornelia M. , Wilson James G. , Jukema J. Wouter , Kiemeney Lambertus , Uitterlinden André G. , Franceschini Nora , North Kari E. , Weir David R. , Metspalu Andres , Boomsma Dorret I. , Hayward Caroline , Chasman Daniel , Martin Nicholas G. , Sattar Naveed , Campbell Harry , Esko Tōnu , Kutalik Zoltán , Wilson James F. 
Published: October 2017

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.