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-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

^*Corresponding author for this work

University of Edinburgh
University of Tartu
Medical University of Graz
National Research Council of Italy
Karolinska Institutet
University of Trieste
IRCCS Ospedale Infantile Burlo Garofolo - Trieste
University of Lausanne
Swiss Institute of Bioinformatics
Mental Health Centre Sct. Hans
The Lundbeck Foundation Initiative for Integrative Psychiatric Research
Queensland Institute of Medical Research
Brigham and Women’s Hospital
University of Amsterdam
University of Michigan, Ann Arbor
Erasmus University Rotterdam
University of Washington
Leiden University
University of Colorado Anschutz Medical Campus
University of North Carolina at Chapel Hill
Radboud University Nijmegen
University College London
Johns Hopkins University
University of Manchester
EURAC Research
University of Lübeck
National Institutes of Health
Tampere University
University of Texas Health Science Center at Houston
Aarhus University
University of Minnesota Twin Cities
Charité – Universitätsmedizin Berlin
University of Glasgow
IRCCS Istituto Neurologico Mediterraneo Neuromed - Pozzilli (IS)
Statens Serum Institut
Gerontology Research Center
Max Planck Institute for Human Development
The University of Auckland
Harvard University
University of Dundee
University of Oslo
Imperial College London
Kaiser Permanente
University of Mississippi
University of Glasgow
Broad Institute

Research output: Contribution to journal › Article › peer-review

132 Citations (Scopus)

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
Article number	910
Journal	Nature Communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00934-5
Publication status	Published - 1 Dec 2017
Externally published	Yes

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10.1038/s41467-017-00934-5

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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

@article{3be9fc4ccc1345ccbc147b540f62bf74,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41467-017-00934-5",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

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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

TY - JOUR

T1 - Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity

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

Y1 - 2017/12/1

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.

UR - https://www.scopus.com/pages/publications/85031691125

U2 - 10.1038/s41467-017-00934-5

DO - 10.1038/s41467-017-00934-5

M3 - Article

C2 - 29030599

AN - SCOPUS:85031691125

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 910

ER -

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

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