Older molecular brain age in severe mental illness.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
27
06
2019
accepted:
25
06
2020
revised:
03
06
2020
pubmed:
8
7
2020
medline:
27
1
2022
entrez:
8
7
2020
Statut:
ppublish
Résumé
Psychiatric disorders are associated with accelerated aging and enhanced risk for neurodegenerative disorders. Brain aging is associated with molecular, cellular, and structural changes that are robust on the group level, yet show substantial inter-individual variability. Here we assessed deviations in gene expression from normal age-dependent trajectories, and tested their validity as predictors of risk for major mental illnesses and neurodegenerative disorders. We performed large-scale gene expression and genotype analyses in postmortem samples of two frontal cortical brain regions from 214 control subjects aged 20-90 years. Individual estimates of "molecular age" were derived from age-dependent genes, identified by robust regression analysis. Deviation from chronological age was defined as "delta age". Genetic variants associated with deviations from normal gene expression patterns were identified by expression quantitative trait loci (cis-eQTL) of age-dependent genes or genome-wide association study (GWAS) on delta age, combined into distinct polygenic risk scores (PRS
Identifiants
pubmed: 32632206
doi: 10.1038/s41380-020-0834-1
pii: 10.1038/s41380-020-0834-1
pmc: PMC7785531
mid: NIHMS1607033
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3646-3656Subventions
Organisme : NIMH NIH HHS
ID : R01 MH109897
Pays : United States
Organisme : NIMH NIH HHS
ID : R37 MH057881
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH084053
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110921
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH066392
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH080405
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046152
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH093723
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG028288
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH075916
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG032984
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG030146
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH103392
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109677
Pays : United States
Organisme : NINR NIH HHS
ID : R01 NR012459
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH097276
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG002219
Pays : United States
Organisme : NIDA NIH HHS
ID : HHSN271201300031C
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA190766
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG028050
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH093725
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005138
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG036836
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085542
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Organisme : NIA NIH HHS
ID : N01 AG062101
Pays : United States
Organisme : NIA NIH HHS
ID : N01 AG062103
Pays : United States
Organisme : NIA NIH HHS
ID : N01 AG062103
Pays : United States
Informations de copyright
© 2020. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Genome Res. 2013 Apr;23(4):716-26
pubmed: 23345460
NPJ Schizophr. 2017 Sep 4;3(1):26
pubmed: 28871179
Schizophr Res. 2018 Jun;196:39-44
pubmed: 28988914
Transl Psychiatry. 2017 Dec 11;7(12):1283
pubmed: 29225347
Dialogues Clin Neurosci. 2013 Mar;15(1):53-65
pubmed: 23576889
Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15605-10
pubmed: 18832152
Biol Psychiatry. 2005 Mar 1;57(5):549-58
pubmed: 15737671
Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):206-11
pubmed: 26699485
Nat Neurosci. 2019 Oct;22(10):1617-1623
pubmed: 31551603
Psychiatry Res. 2018 Nov;269:621-624
pubmed: 30208351
NPJ Schizophr. 2017 Mar 23;3:13
pubmed: 28560259
CMAJ. 2017 Oct 23;189(42):E1304-E1310
pubmed: 29061855
Genome Biol. 2013;14(10):R115
pubmed: 24138928
Prog Neurobiol. 2011 Feb;93(2):165-81
pubmed: 21130140
Transl Psychiatry. 2019 Jan 29;9(1):39
pubmed: 30696804
Mech Ageing Dev. 2018 Oct;175:24-34
pubmed: 29890178
Am J Psychiatry. 2018 Aug 1;175(8):774-782
pubmed: 29656664
Neurobiol Dis. 2011 Feb;41(2):279-90
pubmed: 20887790
Front Psychol. 2015 Sep 16;6:1377
pubmed: 26441752
Neuropsychopharmacology. 2018 Oct;43(11):2277-2284
pubmed: 29849055
Nature. 2004 Jun 24;429(6994):883-91
pubmed: 15190254
Epidemiol Psychiatr Sci. 2019 Nov 07;29:e71
pubmed: 31696818
Schizophr Bull. 2014 Sep;40(5):1140-53
pubmed: 24126515
Schizophr Bull. 2019 Jan 1;45(1):190-198
pubmed: 29272464
Biol Psychiatry. 2019 Feb 1;85(3):257-267
pubmed: 30446205
Nature. 2010 Mar 25;464(7288):536-42
pubmed: 20336136
Neuropsychopharmacology. 2016 Dec;41(13):3080-3091
pubmed: 27417517
Annu Rev Clin Psychol. 2014;10:425-48
pubmed: 24313570