A meta-analysis of genome-wide association studies identifies multiple longevity genes

被引：94

作者：

Deelen, Joris ^{[1
,2
]}

Evans, Daniel S. ^{[3
]}

Arking, Dan E. ^{[4
]}

Tesi, Niccola ^{[5
,6
,7
]}

Nygaard, Marianne ^{[8
]}

Liu, Xiaomin ^{[9
,10
]}

Wojczynski, Mary K. ^{[11
]}

Biggs, Mary L. ^{[12
,13
]}

van Der Spek, Ashley ^{[14
]}

Atzmon, Gil ^{[15
,16
,17
]}

Ware, Erin B. ^{[18
]}

Sarnowski, Chloe ^{[19
]}

Smith, Albert, V ^{[20
,21
]}

Seppala, Ilkka ^{[22
,23
]}

Cordell, Heather J. ^{[24
]}

Dose, Janina ^{[25
]}

Amin, Najaf ^{[14
]}

Arnold, Alice M. ^{[12
]}

Ayers, Kristin L. ^{[26
]}

Barzilai, Nir ^{[16
,17
]}

Becker, Elizabeth J. ^{[27
]}

Beekman, Marian ^{[2
]}

Blanche, Helene ^{[28
]}

Christensen, Kaare ^{[8
,29
,30
]}

Christiansen, Lene ^{[8
,31
]}

Collerton, Joanna C. ^{[32
]}

Cubaynes, Sarah ^{[33
]}

Cummings, Steven R. ^{[3
]}

Davies, Karen ^{[34
]}

Debrabant, Birgit ^{[35
]}

Deleuze, Jean-Francois ^{[28
,36
]}

Duncan, Rachel ^{[32
,37
]}

Faul, Jessica D. ^{[18
]}

Franceschi, Claudio ^{[38
,39
,40
]}

Galan, Pilar ^{[41
]}

Gudnaso, Vilmundur ^{[21
,42
]}

Harris, Tamara B. ^{[43
]}

Huisman, Martijn ^{[44
,45
]}

Hurme, Mikko A. ^{[46
]}

Jagger, Carol ^{[32
,37
]}

Jansen, Iris ^{[5
,47
]}

Jylha, Marja ^{[48
,49
]}

Kahonen, Mika ^{[50
,51
]}

Karasik, David ^{[52
,53
]}

Kardia, Sharon L. R. ^{[54
]}

Kingston, Andrew ^{[32
,37
]}

Kirkwood, Thomas B. L. ^{[37
]}

Launer, Lenore J. ^{[43
]}

Lehtimaki, Terho ^{[22
,23
]}

Lieb, Wolfgang ^{[55
,56
]}

机构：

[1] Max Planck Inst Biol Ageing, D-50866 Cologne, Germany

[2] Leiden Univ, Dept Biomed Data Sci, Med Ctr, Mol Epidemiol, NL-2300 RC Leiden, Netherlands

[3] Calif Pacific Med Ctr Res Inst, San Francisco, CA 94158 USA

[4] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Dept Genet Med, Sch Med, Baltimore, MD 21287 USA

[5] Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Amsterdam Neurosci, Amsterdam, Netherlands

[6] Amsterdam UMC, Dept Clin Genet, NL-1007 MB Amsterdam, Netherlands

[7] Delft Univ Technol, Delft Bioinformat Lab, NL-2600 GA Delft, Netherlands

[8] Univ Southern Denmark, Danish Aging Res Ctr, Dept Publ Hlth, DK-5000 Odense C, Denmark

[9] BGI Shenzhen, Shenzhen 518083, Peoples R China

[10] BGI Shenzhen, China Natl Genebank, Shenzhen 518120, Peoples R China

[11] Washington Univ, Dept Genet, Div Stat Genom, Sch Med, St Louis, MO 63110 USA

[12] Univ Washington, Dept Biostat, Seattle, WA 98115 USA

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

[14] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands

[15] Univ Haifa, Fac Nat Sci, Dept Biol, IL-3498838 Haifa, Israel

[16] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA

[17] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA

[18] Univ Michigan, Survey Res Ctr, Inst Social Res, Ann Arbor, MI 48104 USA

[19] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02118 USA

[20] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA

[21] Icelandic Heart Assoc, IS-201 Kopavogur, Iceland

[22] Tampere Univ, Dept Clin Chem, Fimlab Labs, Fac Med & Hlth Technol, Tampere 33520, Finland

[23] Tampere Univ, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Hlth Technol, Tampere 33520, Finland

[24] Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[25] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany

[26] Sema4, Stamford, CT 06902 USA

[27] Boston Univ, Bioinformat Program, Boston, MA 02118 USA

[28] Fdn Jean Dausset CEPH, F-75010 Paris, France

[29] Odense Univ Hosp, Clin Biochem & Pharmacol, DK-5000 Odense C, Denmark

[30] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark

[31] Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, DK-2100 Copenhagen, Denmark

[32] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England

[33] Univ Montpellier, MMDN, EPHE, Unite Inserm 1198,PSL Res Univ, F-34095 Montpellier, France

[34] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England

[35] Univ Southern Denmark, Dept Publ Hlth, DK-5000 Odense C, Denmark

[36] CEA Inst Biol Francois Jacob, Ctr Natl Rech Genom Humaine, F-91000 Evry, France

[37] Newcastle Univ, Inst Ageing, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England

[38] Lobachevsky State Univ Nizhny Novgorod, Dept Appl Math, Nizhnii Novgorod 603022, Russia

[39] Lobachevsky State Univ Nizhny Novgorod, Ctr Bioinformat, Nizhnii Novgorod 603022, Russia

[40] IRCCS Inst Neurol Sci Bologna ISNB, I-40124 Bologna, Italy

[41] Univ Paris 13, EREN, UMR Inserm U1153, Inra U1125,Cnam Paris 13,CRESS, F-93017 Bobigny, France

[42] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland

[43] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA

[44] Vrije Univ Amsterdam, Dept Epidemiol & Biostat, Amsterdam UMC, NL-1007 MB Amsterdam, Netherlands

[45] Amsterdam Publ Hlth Res Inst, NL-1007 MB Amsterdam, Netherlands

[46] Tampere Univ, Fac Med & Hlth Technol, Dept Microbiol & Immunol, Tampere 33014, Finland

[47] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, NL-1081 HV Amsterdam, Netherlands

[48] Tampere Univ, Fac Social Sci Hlth Sci, Tampere 33104, Finland

[49] Tampere Univ, Gerontol Res Ctr GEREC, Tampere 33104, Finland

[50] Tampere Univ, Dept Clin Physiol, Tampere Univ Hosp, Tampere 33521, Finland

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

LD SCORE REGRESSION; CONFIRMS APOE; LIFE-SPAN; SURVIVAL; HEALTH; LOCUS; GWAS; AGE; HERITABILITY; PREVALENCE;

D O I：

10.1038/s41467-019-11558-2

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：

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) epsilon 4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE epsilon 2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

引用

页数：14

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