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 & 93 others 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 D. 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 Paul 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 A. Kiemeney, André G. Uitterlinden, Nora Franceschini, Kari E. North, David R. Weir, Andres Metspalu, Dorret I. Boomsma, Caroline Hayward, Daniel I. Chasman, Nicholas G. Martin, Naveed Sattar, Harry Campbell, Tōnu Esko, Zoltán Kutalik, James F. Wilson

    Research output: Contribution to journalArticle

    17 Citations (Scopus)
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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 languageEnglish
    Article number910
    Pages (from-to)1-13
    Number of pages13
    JournalNature Communications
    Volume8
    DOIs
    Publication statusPublished - 13 Oct 2017

    Fingerprint

    HLA-DRB1 Chains
    genome
    coronary artery disease
    Meta-Analysis
    Life Style
    Genes
    Education
    Genome
    Coronary Artery Disease
    Apolipoproteins E
    education
    Smoking
    obesity
    Tobacco Products
    HDL Cholesterol
    lipoproteins
    insulin
    Aging of materials
    Genome-Wide Association Study
    Fats

    Keywords

    • Genetics research
    • Genome-wide association studies
    • Quantitative trait

    Cite this

    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 D. ; 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 Paul ; 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 A. ; Uitterlinden, André 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, Tōnu ; Kutalik, Zoltán ; Wilson, James F. / Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. In: Nature Communications. 2017 ; Vol. 8. pp. 1-13.
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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.",
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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, AD, 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, LA, Uitterlinden, AG, Franceschini, N, North, KE, Weir, DR, Metspalu, A, Boomsma, DI, Hayward, C, Chasman, DI, 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, 910, pp. 1-13. https://doi.org/10.1038/s41467-017-00934-5, https://doi.org/10.1038/s41467-017-00934-5

    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; 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 D.; 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 Paul; 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 A.; Uitterlinden, André 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, Tōnu; Kutalik, Zoltán; Wilson, James F.

    In: Nature Communications, Vol. 8, 910, 13.10.2017, p. 1-13.

    Research output: Contribution to journalArticle

    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 D.

    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 Paul

    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 A.

    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 I.

    AU - Martin, Nicholas G.

    AU - Sattar, Naveed

    AU - Campbell, Harry

    AU - Esko, Tōnu

    AU - Kutalik, Zoltán

    AU - Wilson, James F.

    PY - 2017/10/13

    Y1 - 2017/10/13

    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.

    KW - Genetics research

    KW - Genome-wide association studies

    KW - Quantitative trait

    U2 - 10.1038/s41467-017-00934-5

    DO - 10.1038/s41467-017-00934-5

    M3 - Article

    VL - 8

    SP - 1

    EP - 13

    JO - Nature Communications

    JF - Nature Communications

    SN - 2041-1723

    M1 - 910

    ER -