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-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; Tonu Esko; Zoltán Kutalik; James F. Wilson

doi:10.1038/s41467-017-00934-5

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 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, Tonu 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 language	English (US)
Article number	910
Journal	Nature communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00934-5
State	Published - Dec 1 2017

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© 2017 The Author(s).

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715013

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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), Article 910. https://doi.org/10.1038/s41467-017-00934-5

Joshi, PK, Pirastu, N, Kentistou, KA, Fischer, K, Hofer, E, Schraut, KE, Clark, DW, Nutile, T, Barnes, CLK, Timmers, PRHJ, Shen, X, Gandin, I, McDaid, AF, Hansen, TF, Gordon, SD, Giulianini, F, Boutin, TS, Abdellaoui, A, Zhao, W, Medina-Gomez, C, Bartz, TM, Trompet, S, Lange, LA, Raffield, L, Van Der Spek, A, Galesloot, TE, Proitsi, P, Yanek, LR, Bielak, LF, Payton, A, Murgia, F, Concas, MP, Biino, G, Tajuddin, SM, Seppälä, I, Amin, N, Boerwinkle, E, Børglum, AD, Campbell, A, Demerath, EW, Demuth, I, Faul, JD, Ford, I, Gialluisi, A, Gögele, M, Graff, M, Hingorani, A, Hottenga, JJ, Hougaard, DM, Hurme, MA, Ikram, MA, Jylhä, M, Kuh, D, Ligthart, L, Lill, CM, Lindenberger, U, Lumley, T, Mägi, R, Marques-Vidal, P, Medland, SE, Milani, L, Nagy, R, Ollier, WER, Peyser, PA, Pramstaller, PP, Ridker, PM, Rivadeneira, F, Ruggiero, D, Saba, Y, Schmidt, R, Schmidt, H, Slagboom, PE, Smith, BH, Smith, JA, Sotoodehnia, N, Steinhagen-Thiessen, E, Van Rooij, FJA, Verbeek, AL, Vermeulen, SH, Vollenweider, P, Wang, Y, Werge, T, Whitfield, JB, Zonderman, AB, Lehtimäki, T, Evans, MK, Pirastu, M, Fuchsberger, C, Bertram, L, Pendleton, N, Kardia, SLR, Ciullo, M, Becker, DM, Wong, A, Psaty, BM, Van Duijn, CM, Wilson, JG, Jukema, JW, Kiemeney, L, Uitterlinden, AG, Franceschini, N, North, KE, Weir, DR, Metspalu, A, Boomsma, DI, Hayward, C, Chasman, D, Martin, NG, Sattar, N, Campbell, H, Esko, T, Kutalik, Z & Wilson, JF 2017, 'Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity', Nature communications, vol. 8, no. 1, 910. https://doi.org/10.1038/s41467-017-00934-5

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AU - Joshi, Peter K.

AU - Pirastu, Nicola

AU - Kentistou, Katherine A.

AU - Fischer, Krista

AU - Hofer, Edith

AU - Schraut, Katharina E.

AU - Clark, David W.

AU - Nutile, Teresa

AU - Barnes, Catriona L.K.

AU - Timmers, Paul R.H.J.

AU - Shen, Xia

AU - Gandin, Ilaria

AU - McDaid, Aaron F.

AU - Hansen, Thomas Folkmann

AU - Gordon, Scott D.

AU - Giulianini, Franco

AU - Boutin, Thibaud S.

AU - Abdellaoui, Abdel

AU - Zhao, Wei

AU - Medina-Gomez, Carolina

AU - Bartz, Traci M.

AU - Trompet, Stella

AU - Lange, Leslie A.

AU - Raffield, Laura

AU - Van Der Spek, Ashley

AU - Galesloot, Tessel E.

AU - Proitsi, Petroula

AU - Yanek, Lisa R.

AU - Bielak, Lawrence F.

AU - Payton, Antony

AU - Murgia, Federico

AU - Concas, Maria Pina

AU - Biino, Ginevra

AU - Tajuddin, Salman M.

AU - Seppälä, Ilkka

AU - Amin, Najaf

AU - Boerwinkle, Eric

AU - Børglum, Anders D.

AU - Campbell, Archie

AU - Demerath, Ellen W.

AU - Demuth, Ilja

AU - Faul, Jessica D.

AU - Ford, Ian

AU - Gialluisi, Alessandro

AU - Gögele, Martin

AU - Graff, Mariaelisa

AU - Hingorani, Aroon

AU - Hottenga, Jouke Jan

AU - Hougaard, David M.

AU - Hurme, Mikko A.

AU - Ikram, M. Arfan

AU - Jylhä, Marja

AU - Kuh, Diana

AU - Ligthart, Lannie

AU - Lill, Christina M.

AU - Lindenberger, Ulman

AU - Lumley, Thomas

AU - Mägi, Reedik

AU - Marques-Vidal, Pedro

AU - Medland, Sarah E.

AU - Milani, Lili

AU - Nagy, Reka

AU - Ollier, William E.R.

AU - Peyser, Patricia A.

AU - Pramstaller, Peter P.

AU - Ridker, Paul M.

AU - Rivadeneira, Fernando

AU - Ruggiero, Daniela

AU - Saba, Yasaman

AU - Schmidt, Reinhold

AU - Schmidt, Helena

AU - Slagboom, P. Eline

AU - Smith, Blair H.

AU - Smith, Jennifer A.

AU - Sotoodehnia, Nona

AU - Steinhagen-Thiessen, Elisabeth

AU - Van Rooij, Frank J.A.

AU - Verbeek, André L.

AU - Vermeulen, Sita H.

AU - Vollenweider, Peter

AU - Wang, Yunpeng

AU - Werge, Thomas

AU - Whitfield, John B.

AU - Zonderman, Alan B.

AU - Lehtimäki, Terho

AU - Evans, Michele K.

AU - Pirastu, Mario

AU - Fuchsberger, Christian

AU - Bertram, Lars

AU - Pendleton, Neil

AU - Kardia, Sharon L.R.

AU - Ciullo, Marina

AU - Becker, Diane M.

AU - Wong, Andrew

AU - Psaty, Bruce M.

AU - Van Duijn, Cornelia M.

AU - Wilson, James G.

AU - Jukema, J. Wouter

AU - Kiemeney, Lambertus

AU - Uitterlinden, André G.

AU - Franceschini, Nora

AU - North, Kari E.

AU - Weir, David R.

AU - Metspalu, Andres

AU - Boomsma, Dorret I.

AU - Hayward, Caroline

AU - Chasman, Daniel

AU - Martin, Nicholas G.

AU - Sattar, Naveed

AU - Campbell, Harry

AU - Esko, Tonu

AU - Kutalik, Zoltán

AU - Wilson, James F.

PY - 2017/12/1

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N2 - 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.

AB - 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.

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

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