Genome-Wide Meta-Analysis Associates HLA-DQA1/DRB1 and LPA and Lifestyle Factors with Human Longevity

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 M.; 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 A.; Borglum, Anders D.; Campbell, Archie; Demerath, Ellen W.; Demuth, Ilja; Faul, Jessica D.; Ford, Ian; Gialluisi, Alessandro; Gogele, Martin; Graff, Mariaelisa; Hingorani, Aroon; Hottenga, Jouke-Jan; Hougaard, David M.; Hurme, Mikko A.; Ikram, M. Arfan; Jylha, Marja; Kuh, Diana; Ligthart, Lannie; Lill, Christina M.; Lindenberger, Ulman; Lumley, Thomas S.; Magi, 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, Andre L. M.; Vermeulen, Sita H.; Vollenweider, Peter; Wang, Yunpeng; Werge, Thomas; Whitfield, John B.; Zonderman, Alan B.; Lehtimaki, 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, Andre G.; Franceschini, Nora; North, Kari E.; Weir, David R.; Metspalu, Andres; Boomsma, Dorret I.; Hayward, Caroline; Chasman, Daniel I.; Martin, Nicholas G.; Sattar, Naveed; Campbell, Harry; Esko, Tonu; Kutalik, Zoltan; & Wilson, James F. (2017). Genome-Wide Meta-Analysis Associates HLA-DQA1/DRB1 and LPA and Lifestyle Factors with Human Longevity. Nature Communications, 8, 910. PMCID: PMC5715013

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 M.; 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 A.; Borglum, Anders D.; Campbell, Archie; Demerath, Ellen W.; Demuth, Ilja; Faul, Jessica D.; Ford, Ian; Gialluisi, Alessandro; Gogele, Martin; Graff, Mariaelisa; Hingorani, Aroon; Hottenga, Jouke-Jan; Hougaard, David M.; Hurme, Mikko A.; Ikram, M. Arfan; Jylha, Marja; Kuh, Diana; Ligthart, Lannie; Lill, Christina M.; Lindenberger, Ulman; Lumley, Thomas S.; Magi, 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, Andre L. M.; Vermeulen, Sita H.; Vollenweider, Peter; Wang, Yunpeng; Werge, Thomas; Whitfield, John B.; Zonderman, Alan B.; Lehtimaki, 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, Andre G.; Franceschini, Nora; North, Kari E.; Weir, David R.; Metspalu, Andres; Boomsma, Dorret I.; Hayward, Caroline; Chasman, Daniel I.; Martin, Nicholas G.; Sattar, Naveed; Campbell, Harry; Esko, Tonu; Kutalik, Zoltan; & Wilson, James F. (2017). Genome-Wide Meta-Analysis Associates HLA-DQA1/DRB1 and LPA and Lifestyle Factors with Human Longevity. Nature Communications, 8, 910. PMCID: PMC5715013

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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.




JOUR



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 M.
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 A.
Borglum, Anders D.
Campbell, Archie
Demerath, Ellen W.
Demuth, Ilja
Faul, Jessica D.
Ford, Ian
Gialluisi, Alessandro
Gogele, Martin
Graff, Mariaelisa
Hingorani, Aroon
Hottenga, Jouke-Jan
Hougaard, David M.
Hurme, Mikko A.
Ikram, M. Arfan
Jylha, Marja
Kuh, Diana
Ligthart, Lannie
Lill, Christina M.
Lindenberger, Ulman
Lumley, Thomas S.
Magi, 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, Andre L. M.
Vermeulen, Sita H.
Vollenweider, Peter
Wang, Yunpeng
Werge, Thomas
Whitfield, John B.
Zonderman, Alan B.
Lehtimaki, 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, Andre G.
Franceschini, Nora
North, Kari E.
Weir, David R.
Metspalu, Andres
Boomsma, Dorret I.
Hayward, Caroline
Chasman, Daniel I.
Martin, Nicholas G.
Sattar, Naveed
Campbell, Harry
Esko, Tonu
Kutalik, Zoltan
Wilson, James F.



2017


Nature Communications

8


910








PMC5715013


10637

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