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

被引：111

作者：

Joshi, Peter K. ^{[1
]}

Pirastu, Nicola ^{[1
]}

Kentistou, Katherine A. ^{[1
,2
]}

Fischer, Krista ^{[3
]}

Hofer, Edith ^{[4
,5
]}

Schraut, Katharina E. ^{[1
,2
]}

Clark, David W. ^{[1
]}

Nutile, Teresa ^{[6
]}

Barnes, Catriona L. K. ^{[1
]}

Timmers, Paul R. H. J. ^{[1
]}

Shen, Xia ^{[1
,7
]}

Gandin, Ilaria ^{[8
,9
]}

McDaid, Aaron F. ^{[10
,11
]}

Hansen, Thomas Folkmann ^{[12
,13
]}

Gordon, Scott D. ^{[14
]}

Giulianini, Franco ^{[15
]}

Boutin, Thibaud S. ^{[16
]}

Abdellaoui, Abdel ^{[17
]}

Zhao, Wei ^{[18
]}

Medina-Gomez, Carolina ^{[19
,20
]}

Bartz, Traci M. ^{[21
,22
]}

Trompet, Stella ^{[23
,24
]}

Lange, Leslie A. ^{[25
]}

Raffield, Laura ^{[26
]}

van der Spek, Ashley ^{[20
]}

Galesloot, Tessel E. ^{[27
]}

Proitsi, Petroula ^{[28
]}

Yanek, Lisa R. ^{[29
]}

Bielak, Lawrence F. ^{[18
]}

Payton, Antony ^{[30
]}

Murgia, Federico ^{[31
,32
]}

Concas, Maria Pina ^{[33
]}

Biino, Ginevra ^{[34
]}

Tajuddin, Salman M. ^{[35
]}

Seppala, Ilkka ^{[36
,37
]}

Amin, Najaf ^{[20
]}

Boerwinkle, Eric ^{[38
]}

Borglum, Anders D. ^{[13
,39
,40
]}

Campbell, Archie ^{[41
]}

Demerath, Ellen W. ^{[42
]}

Demuth, Ilja ^{[43
,44
,45
]}

Faul, Jessica D. ^{[46
]}

Ford, Ian ^{[47
]}

Gialluisi, Alessandro ^{[48
]}

Gogele, Martin ^{[31
,32
]}

Graff, MariaElisa ^{[49
]}

Hingorani, Aroon ^{[50
]}

Hottenga, Jouke-Jan ^{[17
]}

Hougaard, David M. ^{[13
,51
]}

Hurme, Mikko A. ^{[37
,52
]}

机构：

[1] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh EH8 9AG, Midlothian, Scotland

[2] Univ Edinburgh, Queens Med Res Inst, Ctr Cardiovasc Sci, Edinburgh EH16 4TJ, Midlothian, Scotland

[3] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia

[4] Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, A-8036 Graz, Austria

[5] Med Univ Graz, Inst Med Informat Stat & Documentat, A-8036 Graz, Austria

[6] Inst Genet & Biophys A Buzzati Traverso, CNR, I-80131 Naples, Italy

[7] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden

[8] Univ Trieste, Dept Med Sci, I-34100 Trieste, Italy

[9] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, I-34137 Trieste, Italy

[10] Lausanne Univ Hosp, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland

[11] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland

[12] Mental Hlth Ctr Sct Hans, Mental Hlth Serv Copenhagen, Inst Biol Psychiat, DK-4000 Roskilde, Denmark

[13] Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, DK-8000 Aarhus, Denmark

[14] QIMR Berghofer Inst Med Res, Brisbane, Qld 4006, Australia

[15] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA

[16] Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Crewe Rd, Edinburgh EH4 2XU, Midlothian, Scotland

[17] Vrije Univ Amsterdam, Amsterdam Publ Hlth Inst APH, Dept Biol Psychol, Netherlands Twin Register, NL-1081BT Amsterdam, Netherlands

[18] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA

[19] Erasmus Univ, Med Ctr, Dept Internal Med, NL-3015 CN Rotterdam, Netherlands

[20] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3015 Rotterdam, Netherlands

[21] Univ Washington, Cardiovasc Hlth Res Unit, Dept Biostat, Seattle, WA 98101 USA

[22] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA

[23] Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, NL-2300RC Leiden, Netherlands

[24] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300RC Leiden, Netherlands

[25] Univ Colorado Denver, Anschutz Med Campus, Dept Med, Aurora, CO 80045 USA

[26] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[27] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Hlth Evidence, NL-6500 HB Nijmegen, Netherlands

[28] UCL, MRC Unit Lifelong Hlth & Ageing UCL, London WC1B 5JU, England

[29] Johns Hopkins Univ, Sch Med, GeneSTAR Res Program, Dept Med, Baltimore, MD 21287 USA

[30] Univ Manchester, Ctr Epidemiol, Div Populat Hlth Hlth Serv Res & Primary Care, Manchester M13 9PL, Lancs, England

[31] European Acad Bozen Bolzano EURAC, Ctr Biomed, I-39100 Bolzano, Italy

[32] Univ Lubeck, Affiliated Inst, Lubeck, Germany

[33] Natl Res Council Italy, Inst Genet & Biomed Res Support Unity, I-07100 Sassari, Italy

[34] Natl Res Council Italy, Inst Mol Genet, I-27100 Pavia, Italy

[35] NIA, NIH, Lab Epidemiol & Populat Sci, Baltimore, MD 21224 USA

[36] Univ Tampere, Fimlab Lab, Dept Clin Chem, Tampere 33014, Finland

[37] Univ Tampere, Fac Med & Life Sci, Tampere 33014, Finland

[38] Univ Texas Houston, Hlth Sci Ctr Houston, UTHlth Sch Publ, Houston, TX 77030 USA

[39] Aarhus Univ, Dept Biomed Human Genet, DK-8000 Aarhus, Denmark

[40] Aarhus Univ, Ctr Integrat Sequencing, iSEQ, DK-8000 Aarhus, Denmark

[41] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland

[42] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA

[43] Univ Med Berlin, Res Grp Geriatr, Charite, D-13347 Berlin, Germany

[44] Univ Med Berlin, Interdisciplinary Metab Ctr, Lipid Clin, Charite, D-13353 Berlin, Germany

[45] Univ Med Berlin, Inst Med & Human Genet, Charite, D-13353 Berlin, Germany

[46] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48014 USA

[47] Univ Glasgow, Robertson Ctr Biostat, Glasgow G12 8QQ, Lanark, Scotland

[48] IRCCS Neuromed, I-86077 Pozzilli, IS, Italy

[49] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27514 USA

[50] UCL, Inst Cardiovasc Sci, London WC1E 6BT, England

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

SUSCEPTIBILITY LOCI; GENETIC-VARIANTS; BLOOD-PRESSURE; SURVIVAL; RISK; AGE; POPULATION; DISEASE; INDIVIDUALS; APOE;

D O I：

10.1038/s41467-017-00934-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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