Defining functional variants associated with Alzheimer's disease in the induced immune response.
Alzheimer's disease
TWAS
lipid metabolism
mitochondria
monocytes
Journal
Brain communications
ISSN: 2632-1297
Titre abrégé: Brain Commun
Pays: England
ID NLM: 101755125
Informations de publication
Date de publication:
2021
2021
Historique:
received:
07
09
2020
revised:
17
03
2021
accepted:
22
03
2021
entrez:
7
5
2021
pubmed:
8
5
2021
medline:
8
5
2021
Statut:
epublish
Résumé
Defining the mechanisms involved in the aetiology of Alzheimer's disease from genome-wide association studies alone is challenging since Alzheimer's disease is polygenic and most genetic variants are non-coding. Non-coding Alzheimer's disease risk variants can influence gene expression by affecting miRNA binding and those located within enhancers and within CTCF sites may influence gene expression through alterations in chromatin states. In addition, their function can be cell-type specific. They can function specifically in microglial enhancers thus affecting gene expression in the brain. Hence, transcriptome-wide association studies have been applied to test the genetic association between disease risk and cell-/tissue-specific gene expression. Many Alzheimer's disease-associated loci are involved in the pathways of the innate immune system. Both microglia, the primary immune cells of the brain, and monocytes which can infiltrate the brain and differentiate into activated macrophages, have roles in neuroinflammation and β-amyloid clearance through phagocytosis. In monocytes the function of regulatory variants can be context-specific after immune stimulation. To dissect the variants associated with Alzheimer's disease in the context of monocytes, we utilized data from naïve monocytes and following immune stimulation
Identifiants
pubmed: 33959712
doi: 10.1093/braincomms/fcab083
pii: fcab083
pmc: PMC8087896
doi:
Types de publication
Journal Article
Langues
eng
Pagination
fcab083Subventions
Organisme : Medical Research Council
ID : MC_PC_17112
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : N01AG12100
Pays : United States
Organisme : Medical Research Council
ID : G0902227
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG032984
Pays : United States
Organisme : Medical Research Council
ID : MR/M009076/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T04604X/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG033193
Pays : United States
Organisme : Medical Research Council
ID : G0600237
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0300429
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L501517/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Organisme : Medical Research Council
ID : G0801418
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : Medical Research Council
ID : MR/K013041/1
Pays : United Kingdom
Informations de copyright
© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.
Références
Nat Commun. 2015 Jul 07;6:7545
pubmed: 26151758
Cell Tissue Res. 1998 Nov;294(2):309-21
pubmed: 9799447
Mol Nutr Food Res. 2019 Oct;63(20):e1900183
pubmed: 31325205
PLoS One. 2010 Nov 15;5(11):e13950
pubmed: 21085570
Nat Protoc. 2010 Sep;5(9):1564-73
pubmed: 21085122
Genome Med. 2018 Feb 26;10(1):14
pubmed: 29482603
Nat Genet. 2015 Sep;47(9):1091-8
pubmed: 26258848
Brain. 2015 Dec;138(Pt 12):3673-84
pubmed: 26490334
Cell. 2016 Nov 17;167(5):1398-1414.e24
pubmed: 27863251
EBioMedicine. 2015 Nov;2(11):1619-26
pubmed: 26870787
Twin Res Hum Genet. 2010 Jun;13(3):231-45
pubmed: 20477721
Nat Genet. 2016 May;48(5):481-7
pubmed: 27019110
Pac Symp Biocomput. 2019;24:296-307
pubmed: 30864331
Nat Genet. 2011 May;43(5):436-41
pubmed: 21460841
Nucleic Acids Res. 2016 Feb 29;44(4):1813-32
pubmed: 26826708
BMC Bioinformatics. 2011 Aug 04;12:322
pubmed: 21816037
Nat Genet. 2013 Dec;45(12):1452-8
pubmed: 24162737
Nat Genet. 2016 Mar;48(3):245-52
pubmed: 26854917
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Nature. 1991 Feb 21;349(6311):704-6
pubmed: 1671712
PLoS Comput Biol. 2015 Apr 17;11(4):e1004219
pubmed: 25885710
J Cell Biol. 2003 Apr 14;161(1):41-54
pubmed: 12695498
Nat Commun. 2018 May 8;9(1):1825
pubmed: 29739930
JAMA. 1997 Oct 22-29;278(16):1349-56
pubmed: 9343467
Am J Pathol. 1998 Jan;152(1):307-17
pubmed: 9422548
Nat Genet. 2011 May;43(5):429-35
pubmed: 21460840
PLoS One. 2014 Apr 17;9(4):e95152
pubmed: 24743338
Transl Psychiatry. 2018 May 18;8(1):99
pubmed: 29777097
Nat Commun. 2017 Jul 31;8(1):162
pubmed: 28757615
BMC Med Genomics. 2019 Sep 9;12(1):128
pubmed: 31500627
Trends Immunol. 2018 May;39(5):380-392
pubmed: 29478771
Gigascience. 2015 Feb 25;4:7
pubmed: 25722852
Science. 2014 May 2;344(6183):519-23
pubmed: 24786080
Genomics. 1993 Jul;17(1):171-84
pubmed: 8104867
Science. 1993 Aug 13;261(5123):921-3
pubmed: 8346443
Hum Mol Genet. 1996 Jul;5(7):985-8
pubmed: 8817335
Nat Genet. 2017 Sep;49(9):1373-1384
pubmed: 28714976
Virus Res. 2017 Oct 15;242:1-6
pubmed: 28870470
Front Immunol. 2018 Jul 12;9:1605
pubmed: 30050539
Nature. 2015 Feb 19;518(7539):317-30
pubmed: 25693563
Nat Commun. 2019 Jul 25;10(1):3310
pubmed: 31346172
PLoS One. 2019 Jul 8;14(7):e0218111
pubmed: 31283791
Nat Neurosci. 2020 Mar;23(3):311-322
pubmed: 32112059
PLoS Med. 2009 Feb 3;6(2):e22
pubmed: 19192942
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
Elife. 2019 Feb 18;8:
pubmed: 30775970
J Exp Med. 2004 May 17;199(10):1331-41
pubmed: 15136589
PLoS One. 2010 May 18;5(5):e10693
pubmed: 20502693
Nat Genet. 2017 Jan;49(1):139-145
pubmed: 27918533
Br J Pharmacol. 2019 Sep;176(18):3489-3507
pubmed: 30675901
Sci Transl Med. 2019 Aug 14;11(505):
pubmed: 31413141
Am J Hum Genet. 2013 Nov 7;93(5):779-97
pubmed: 24210251
PLoS Genet. 2013;9(1):e1003240
pubmed: 23382694
Science. 2014 Mar 7;343(6175):1246949
pubmed: 24604202
Front Mol Neurosci. 2020 Aug 21;13:160
pubmed: 32973449
Ann Clin Transl Neurol. 2019 Feb 18;6(3):456-465
pubmed: 30911569
Nat Genet. 2019 Mar;51(3):568-576
pubmed: 30804563
Nat Neurosci. 2017 Aug;20(8):1052-1061
pubmed: 28628103
Science. 2003 Dec 5;302(5651):1760-5
pubmed: 14615545
Mitochondrion. 2019 Nov;49:35-45
pubmed: 31288090
Mol Neurodegener. 2017 Nov 6;12(1):82
pubmed: 29110684
PLoS One. 2012;7(11):e50976
pubmed: 23226438
Nat Genet. 2019 Mar;51(3):414-430
pubmed: 30820047
Glia. 2019 Oct;67(10):1958-1975
pubmed: 31301160
J Neuropathol Exp Neurol. 2001 Aug;60(8):759-67
pubmed: 11487050
Nature. 1995 Jun 29;375(6534):754-60
pubmed: 7596406
Nat Genet. 2009 Oct;41(10):1094-9
pubmed: 19734903
Nat Genet. 2012 Mar 25;44(5):502-10
pubmed: 22446964
Int J Epidemiol. 2008 Dec;37(6):1220-6
pubmed: 18263651
Science. 2019 Nov 29;366(6469):1134-1139
pubmed: 31727856