Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity
Creators: name: Hofer, Edith
name: Schmidt, Reinhold
name: Ikram, M. Arfan
name: Lumley, Thomas
name: Wilson, James G.
name: Nagy, Reka
name: Graff, Mariaelisa
name: Boomsma, Dorret I.
name: Proitsi, Petroula
name: Barnes, Catriona L. K.
name: Whitfield, John B.
name: McDaid, Aaron F.
name: Ciullo, Marina
name: Kuh, Diana
name: Rivadeneira, Fernando
name: Uitterlinden, André G.
name: Saba, Yasaman
name: Kiemeney, Lambertus
name: Kutalik, Zoltán
name: Tajuddin, Salman M.
name: Kentistou, Katherine A.
name: Galesloot, Tessel E.
name: Biino, Ginevra
name: Milani, Lili
name: Wilson, James F.
name: Franceschini, Nora
name: Van Rooij, Frank J. A.
name: Hougaard, David M.
name: Hurme, Mikko A.
name: Zhao, Wei
name: Lindenberger, Ulman
name: Gordon, Scott D.
name: Van Duijn, Cornelia M.
name: Schmidt, Helena
name: Nutile, Teresa
name: Børglum, Anders D.
name: Pirastu, Nicola
name: Vermeulen, Sita H.
name: Metspalu, Andres
name: Ford, Ian
name: Fuchsberger, Christian
name: Schraut, Katharina E.
name: North, Kari E.
name: Becker, Diane M.
name: Werge, Thomas
name: Boerwinkle, Eric
name: Vollenweider, Peter
name: Smith, Blair H.
name: Payton, Antony
name: Wong, Andrew
name: Kardia, Sharon L. R.
name: Abdellaoui, Abdel
name: Fischer, Krista
name: Hottenga, Jouke-Jan
name: Van Der Spek, Ashley
name: Pendleton, Neil
name: Joshi, Peter K.
name: Mägi, Reedik
name: Yanek, Lisa R.
name: Chasman, Daniel
name: Bielak, Lawrence F.
name: Giulianini, Franco
name: Verbeek, André L.
name: Sotoodehnia, Nona
name: Lehtimäki, Terho
name: Bertram, Lars
name: Peyser, Patricia A.
name: Martin, Nicholas G.
name: Timmers, Paul R. H. J.
name: Zonderman, Alan B.
name: Ollier, William E. R.
name: Raffield, Laura
name: Lange, Leslie A.
name: Shen, Xia
name: Lill, Christina M.
name: Concas, Maria Pina
name: Pramstaller, Peter P.
name: Jylhä, Marja
name: Steinhagen-Thiessen, Elisabeth
name: Evans, Michele K.
name: Amin, Najaf
name: Medland, Sarah E.
name: Hingorani, Aroon
name: Gögele, Martin
name: Pirastu, Mario
name: Trompet, Stella
name: Smith, Jennifer A.
name: Gialluisi, Alessandro
name: Jukema, J. Wouter
name: Ridker, Paul M.
name: Gandin, Ilaria
name: Boutin, Thibaud S.
name: Campbell, Archie
name: Medina-Gomez, Carolina
name: Demuth, Ilja
name: Faul, Jessica D.
name: Murgia, Federico
name: Clark, David W.
name: Marques-Vidal, Pedro
name: Weir, David R.
name: Hansen, Thomas Folkmann
name: Sattar, Naveed
name: Hayward, Caroline
name: Esko, Tonu
name: Seppälä, Ilkka
name: Campbell, Harry
name: Wang, Yunpeng
name: Ruggiero, Daniela
name: Demerath, Ellen W.
name: Slagboom, P. Eline
name: Bartz, Traci M.
name: Ligthart, Lannie
name: Psaty, Bruce M.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2017

description: 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.