Meta-analysis of age-related cognitive decline reveals a novel locus for the attention domain and implicates a COVID-19-related gene for global cognitive function.
APOE
GWAS
TMPRSS11D
cognitive decline
meta-analysis
neurocognitive domains
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
01
03
2023
received:
19
10
2022
accepted:
08
03
2023
pmc-release:
01
11
2024
medline:
16
11
2023
pubmed:
24
4
2023
entrez:
24
04
2023
Statut:
ppublish
Résumé
Cognitive abilities have substantial heritability throughout life, as shown by twin- and population-based studies. However, there is limited understanding of the genetic factors related to cognitive decline in aging across neurocognitive domains. We conducted a meta-analysis on 3045 individuals aged ≥65, derived from three population-based cohorts, to identify genetic variants associated with the decline of five neurocognitive domains (attention, memory, executive function, language, visuospatial function) and global cognitive decline. We also conducted gene-based and functional bioinformatics analyses. Apolipoprotein E (APOE)4 was significantly associated with decline of memory (p = 5.58E-09) and global cognitive function (p = 1.84E-08). We identified a novel association with attention decline on chromosome 9, rs6559700 (p = 2.69E-08), near RASEF. Gene-based analysis also identified a novel gene, TMPRSS11D, involved in the activation of SARS-CoV-2, to be associated with the decline in global cognitive function (p = 4.28E-07). Domain-specific genetic studies can aid in the identification of novel genes and pathways associated with decline across neurocognitive domains. rs6559700 was associated with decline of attention. APOE4 was associated with decline of memory and global cognitive decline. TMPRSS11D, a gene involved in the activation of SARS-CoV-2, was implicated in global cognitive decline. Cognitive domain abilities had both unique and shared molecular pathways across the domains.
Identifiants
pubmed: 37089073
doi: 10.1002/alz.13064
pmc: PMC10590825
mid: NIHMS1888134
doi:
Substances chimiques
Apolipoprotein E4
0
Types de publication
Meta-Analysis
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5010-5022Subventions
Organisme : NIA NIH HHS
ID : R01 AG064877
Pays : United States
Organisme : NIA NIH HHS
ID : R37 AG023651
Pays : United States
Organisme : NIH HHS
ID : AG007562
Pays : United States
Organisme : NIH HHS
ID : AG023651
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG064877
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066468
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG041718
Pays : United States
Organisme : NIH HHS
ID : AG041718
Pays : United States
Organisme : NIH HHS
ID : U01 AT000162
Pays : United States
Organisme : NCCIH NIH HHS
ID : U01 AT000162
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : NIH HHS
ID : AG030653
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG023651
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG030653
Pays : United States
Organisme : NIH HHS
ID : AG064877
Pays : United States
Informations de copyright
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Références
Br J Psychiatry. 1980 Jan;136:40-5
pubmed: 7357220
Nat Rev Neurol. 2014 Nov;10(11):634-42
pubmed: 25266297
Neurotherapeutics. 2022 Jan;19(1):152-172
pubmed: 34935119
Mol Psychiatry. 2017 Mar;22(3):336-345
pubmed: 28093568
Nature. 2022 Apr;604(7907):697-707
pubmed: 35255491
Mol Psychiatry. 2016 Feb;21(2):189-197
pubmed: 25869804
Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):13790-4
pubmed: 25201988
Genome Res. 2012 Sep;22(9):1790-7
pubmed: 22955989
Front Neurol. 2021 Jul 29;12:699582
pubmed: 34393978
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
Am J Physiol Lung Cell Mol Physiol. 2017 May 1;312(5):L657-L668
pubmed: 28235951
Genes Dev. 2017 Aug 1;31(15):1509-1528
pubmed: 28912172
Int J Geriatr Psychiatry. 2009 Nov;24(11):1277-84
pubmed: 19340894
NPJ Aging Mech Dis. 2021 Feb 4;7(1):3
pubmed: 33542243
Transl Psychiatry. 2020 Jul 22;10(1):245
pubmed: 32699239
J Alzheimers Dis. 2020;74(1):139-149
pubmed: 31985465
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
PLoS Comput Biol. 2015 Apr 17;11(4):e1004219
pubmed: 25885710
Physiol Rev. 2021 Jul 1;101(3):1309-1370
pubmed: 33000986
J Virol. 2021 Mar 24;95(11):
pubmed: 33762412
Nature. 2020 May;581(7806):71-76
pubmed: 32376954
Dev Psychol. 2011 Mar;47(2):331-43
pubmed: 21244145
Neurobiol Aging. 2011 Jan;32(1):63-74
pubmed: 19285755
Am J Alzheimers Dis Other Demen. 2010 Aug;25(5):432-8
pubmed: 20660517
Nat Genet. 2016 Oct;48(10):1284-1287
pubmed: 27571263
Neuropsychol Rev. 2015 Mar;25(1):97-112
pubmed: 25732892
Nat Commun. 2018 May 29;9(1):2098
pubmed: 29844566
Sci Rep. 2018 Dec 4;8(1):17624
pubmed: 30514932
Am J Manag Care. 2020 Aug;26(8 Suppl):S177-S183
pubmed: 32840331
Nat Genet. 2015 Jul;47(7):702-9
pubmed: 25985137
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Lancet Neurol. 2018 Jun;17(6):548-558
pubmed: 29724592
Am J Hum Genet. 2018 Nov 1;103(5):691-706
pubmed: 30388399
Alzheimers Res Ther. 2021 Jan 4;13(1):5
pubmed: 33397450
Nat Commun. 2017 Nov 28;8(1):1826
pubmed: 29184056
Science. 1997 Jun 6;276(5318):1560-3
pubmed: 9171059
JAMA. 2008 Nov 19;300(19):2253-62
pubmed: 19017911
Nucleic Acids Res. 2019 Jan 8;47(D1):D886-D894
pubmed: 30371827
Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):19006-11
pubmed: 24191011
Nat Genet. 2018 Aug;50(8):1112-1121
pubmed: 30038396
Curr Opin Virol. 2015 Jun;12:15-9
pubmed: 25676874
Schizophr Res. 2018 Nov;201:393-399
pubmed: 29907492
J Gerontol A Biol Sci Med Sci. 2020 Sep 25;75(10):1863-1873
pubmed: 32396611
Mol Psychiatry. 2014 Jan;19(1):76-87
pubmed: 23207651
Nat Genet. 2019 Mar;51(3):414-430
pubmed: 30820047
Am J Hum Genet. 2007 Sep;81(3):559-75
pubmed: 17701901
Hum Genet. 2020 Apr;139(4):499-512
pubmed: 31980904
Sci Adv. 2021 Jul 28;7(31):
pubmed: 34321199
J Biol Chem. 2017 Dec 15;292(50):20669-20682
pubmed: 29054928
Annu Rev Cell Dev Biol. 2011;27:213-35
pubmed: 21721945
J Alzheimers Dis. 2022;88(2):787-798
pubmed: 35694926
Viruses. 2021 Feb 28;13(3):
pubmed: 33671076
Mol Neurodegener. 2018 Oct 4;13(1):52
pubmed: 30286791
PLoS One. 2017 Aug 11;12(8):e0182448
pubmed: 28800603
Innov Aging. 2020 Jun 30;4(3):igaa015
pubmed: 32665981
Nucleic Acids Res. 2020 Jan 8;48(D1):D983-D991
pubmed: 31598699
Neurobiol Aging. 2012 May;33(5):1017.e1-15
pubmed: 22054870
Neurobiol Aging. 2019 Dec;84:239.e15-239.e24
pubmed: 30954325
J Alzheimers Dis. 2022;88(3):1061-1074
pubmed: 35723106
Sci Rep. 2019 Dec 2;9(1):18085
pubmed: 31792241