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; Thomas Werge; Tõnu Esko; Zoltan Kutalik; James F Wilson; et al.

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, Thomas Werge, Tõnu Esko, Zoltan Kutalik, James F Wilson, et al.

Department of Clinical Medicine

61 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 language	English
Article number	910
Journal	Nature Communications
Volume	8
Number of pages	13
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-017-00934-5
Publication status	Published - 1 Dec 2017

Keywords

Alleles
Body Mass Index
Coronary Disease/blood
Education
Genetic Predisposition to Disease/genetics
Genome-Wide Association Study
HLA-DQ alpha-Chains/genetics
HLA-DRB1 Chains/genetics
Humans
Insulin Resistance/genetics
Life Style
Lipoprotein(a)/genetics
Lipoproteins, HDL/blood
Longevity/genetics
Lung Neoplasms/blood
Obesity/complications
Polymorphism, Single Nucleotide
Smoking/adverse effects
Socioeconomic Factors

UN SDGs

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

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10.1038/s41467-017-00934-5Licence: CC BY

Genome-wide meta-analysis associates HLADQA1/ DRB1 and LPA and lifestyle factors with human longevityFinal published version, 4.23 MBLicence: CC BY

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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., ... et al. (2017). Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. Nature Communications, 8, [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, J-J, Hougaard, DM, Werge, T, Esko, T, Kutalik, Z, Wilson, JF & et al. 2017, 'Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity', Nature Communications, vol. 8, 910. https://doi.org/10.1038/s41467-017-00934-5

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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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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 - Werge, Thomas

AU - Esko, Tõnu

AU - Kutalik, Zoltan

AU - Wilson, James F

AU - et al.

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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.

KW - Alleles

KW - Body Mass Index

KW - Coronary Disease/blood

KW - Education

KW - Genetic Predisposition to Disease/genetics

KW - Genome-Wide Association Study

KW - HLA-DQ alpha-Chains/genetics

KW - HLA-DRB1 Chains/genetics

KW - Humans

KW - Insulin Resistance/genetics

KW - Life Style

KW - Lipoprotein(a)/genetics

KW - Lipoproteins, HDL/blood

KW - Longevity/genetics

KW - Lung Neoplasms/blood

KW - Obesity/complications

KW - Polymorphism, Single Nucleotide

KW - Smoking/adverse effects

KW - Socioeconomic Factors

U2 - 10.1038/s41467-017-00934-5

DO - 10.1038/s41467-017-00934-5

M3 - Journal article

C2 - 29030599

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 910

ER -

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

Abstract

Keywords

UN SDGs

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