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.

Institut for Klinisk Medicin

61 Citationer (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.

Originalsprog	Engelsk
Artikelnummer	910
Tidsskrift	Nature Communications
Vol/bind	8
Antal sider	13
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-017-00934-5
Status	Udgivet - 1 dec. 2017

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

Genome-wide meta-analysis associates HLADQA1/ DRB1 and LPA and lifestyle factors with human longevityForlagets udgivne version, 4,23 MBLicens: 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, bind 8, 910. https://doi.org/10.1038/s41467-017-00934-5

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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.",

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",

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 Jouke-Jan Hottenga and Hougaard, {David M} and Thomas Werge and T{\~o}nu Esko and Zoltan Kutalik and Wilson, {James F} and {et al.}",

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

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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 - Werge, Thomas

AU - Esko, Tõnu

AU - Kutalik, Zoltan

AU - Wilson, James F

AU - et al.

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.

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

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