A meta-analysis of genome-wide association studies identifies multiple longevity genes.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 08 2019
14 08 2019
Historique:
received:
31
12
2018
accepted:
17
07
2019
entrez:
16
8
2019
pubmed:
16
8
2019
medline:
18
12
2019
Statut:
epublish
Résumé
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) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) 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.
Identifiants
pubmed: 31413261
doi: 10.1038/s41467-019-11558-2
pii: 10.1038/s41467-019-11558-2
pmc: PMC6694136
doi:
Substances chimiques
Apolipoprotein E2
0
Apolipoprotein E4
0
Endoplasmic Reticulum Chaperone BiP
0
HSPA5 protein, human
0
Heat-Shock Proteins
0
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
3669Subventions
Organisme : Wellcome Trust
ID : 102858/Z/13/Z
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL120393
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL130114
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002369
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL120393
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NIH HHS
ID : S10 OD016290
Pays : United States
Organisme : Medical Research Council
ID : G0500997
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG023746
Pays : United States
Organisme : NIMHD NIH HHS
ID : L60 MD012145
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG055406
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG051129
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG063893
Pays : United States
Organisme : Medical Research Council
ID : MR/J50001X/1
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Références
J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1453-1464
pubmed: 28329165
Nat Commun. 2018 May 8;9(1):1825
pubmed: 29739930
Genetics. 2018 Nov;210(3):1109-1124
pubmed: 30401766
Annu Rev Genomics Hum Genet. 2000;1:507-37
pubmed: 11701639
Am J Hum Genet. 2011 May 13;88(5):586-98
pubmed: 21565292
PLoS Genet. 2014 May 15;10(5):e1004383
pubmed: 24830394
Circulation. 2011 Nov 8;124(19):2145-54
pubmed: 22064958
Exp Gerontol. 2014 May;53:16-23
pubmed: 24534555
J Gerontol A Biol Sci Med Sci. 2018 Oct 8;73(11):1472-1481
pubmed: 30299504
J Gerontol A Biol Sci Med Sci. 2012 Apr;67(4):395-405
pubmed: 22219514
Hum Mol Genet. 2014 Aug 15;23(16):4420-32
pubmed: 24688116
J Mol Neurosci. 2004;23(3):189-204
pubmed: 15181247
Aging Cell. 2011 Aug;10(4):686-98
pubmed: 21418511
Diabetologia. 2001 Jan;44(1):3-15
pubmed: 11206408
Nat Genet. 2013 Jan;45(1):25-33
pubmed: 23202125
Nat Protoc. 2014 May;9(5):1192-212
pubmed: 24762786
Elife. 2019 Jan 15;8:
pubmed: 30642433
Nat Commun. 2019 Jan 7;10(1):35
pubmed: 30617297
Exp Gerontol. 2014 Sep;57:41-6
pubmed: 24809632
Cell. 2013 Jun 6;153(6):1194-217
pubmed: 23746838
Sci Rep. 2017 Jun 12;7(1):3292
pubmed: 28607446
Nat Commun. 2017 Jul 27;8:15842
pubmed: 28748955
Nat Genet. 2015 Mar;47(3):291-5
pubmed: 25642630
Mech Ageing Dev. 2017 Jul;165(Pt B):139-146
pubmed: 28143747
J Gerontol A Biol Sci Med Sci. 2017 Oct 1;72(10):1401-1406
pubmed: 27707806
Nucleic Acids Res. 2018 Jun 20;46(11):5587-5600
pubmed: 29733381
Nat Commun. 2017 Dec 12;8(1):2063
pubmed: 29234056
Mech Ageing Dev. 2011 Jun-Jul;132(6-7):324-30
pubmed: 21740922
J Gerontol A Biol Sci Med Sci. 2019 Jan 1;74(1):44-51
pubmed: 30060062
Mech Ageing Dev. 2016 Apr;155:7-9
pubmed: 26930295
Nat Genet. 1994 Jan;6(1):29-32
pubmed: 8136829
J Am Geriatr Soc. 2009 Sep;57(9):1634-7
pubmed: 19682117
Cell Cycle. 2008 Sep 15;7(18):2795-802
pubmed: 18769141
Commun Biol. 2019 Jan 30;2:41
pubmed: 30729179
JAMA Netw Open. 2018 Aug;1(4):e181670
pubmed: 30294719
Aging Cell. 2016 Jun;15(3):585-8
pubmed: 27004735
Nat Genet. 2011 Mar 06;43(4):333-8
pubmed: 21378990
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
Science. 2002 May 10;296(5570):1029-31
pubmed: 12004104
J Gerontol A Biol Sci Med Sci. 2010 May;65(5):478-87
pubmed: 20304771
Nature. 2019 Jun;570(7762):514-518
pubmed: 31217584
Aging (Albany NY). 2017 Dec 6;9(12):2504-2520
pubmed: 29227965
Nature. 2018 Sep;561(7721):45-56
pubmed: 30185958
Bioinformatics. 2016 Oct 15;32(20):3207-3209
pubmed: 27318201
Nat Commun. 2017 Oct 13;8(1):910
pubmed: 29030599
Bioinformatics. 2017 Jan 15;33(2):272-279
pubmed: 27663502
BMC Med. 2015 Sep 15;13:222
pubmed: 26373927
JAMA. 2014 Jan 8;311(2):183-92
pubmed: 24399557
Aging (Albany NY). 2011 Jan;3(1):63-76
pubmed: 21258136
J Gerontol A Biol Sci Med Sci. 2015 Jan;70(1):110-8
pubmed: 25199915
Science. 2018 Apr 13;360(6385):171-175
pubmed: 29496957
Nat Genet. 2014 Mar;46(3):234-44
pubmed: 24509480
BMB Rep. 2016 Nov;49(11):623-628
pubmed: 27697106
Nature. 2009 May 21;459(7245):356-63
pubmed: 19458711
Age (Dordr). 2014 Apr;36(2):945-7
pubmed: 24271844
Sci Rep. 2016 Feb 25;6:21243
pubmed: 26912274
J Gerontol A Biol Sci Med Sci. 2016 Mar;71(3):340-6
pubmed: 25814633
Aging Cell. 2012 Oct;11(5):727-31
pubmed: 22888763
Ageing Res Rev. 2017 Sep;38:28-39
pubmed: 28689042
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
pubmed: 12883005