QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
04 Mar 2024
04 Mar 2024
Historique:
received:
08
06
2023
accepted:
12
02
2024
medline:
6
3
2024
pubmed:
5
3
2024
entrez:
4
3
2024
Statut:
epublish
Résumé
DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration. Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of macular degeneration pathology by genotype-environment interaction in retina.
Identifiants
pubmed: 38438351
doi: 10.1038/s41467-024-46063-8
pii: 10.1038/s41467-024-46063-8
pmc: PMC10912779
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1972Subventions
Organisme : Intramural NIH HHS
ID : ZIA EY000450
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY031424
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY014104
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY028554
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA EY000546
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
Références
Nat Genet. 2016 May;48(5):481-7
pubmed: 27019110
Mutat Res. 2008 Feb 1;638(1-2):184-94
pubmed: 18035380
Hum Mol Genet. 2020 Jul 29;29(12):2022-2034
pubmed: 32246154
Redox Biol. 2017 Oct;13:255-265
pubmed: 28600982
Cell Rep. 2020 Apr 21;31(3):107525
pubmed: 32320661
Nat Genet. 2006 Aug;38(8):904-9
pubmed: 16862161
Nature. 2009 Oct 8;461(7265):747-53
pubmed: 19812666
Bioinformatics. 2012 Mar 15;28(6):882-3
pubmed: 22257669
Nat Rev Genet. 2020 Feb;21(2):88-101
pubmed: 31690828
Nat Rev Dis Primers. 2021 May 6;7(1):31
pubmed: 33958600
Genome Biol. 2021 Apr 30;22(1):127
pubmed: 33931130
Biotechniques. 1993 Sep;15(3):532-4, 536-7
pubmed: 7692896
Nat Genet. 2023 Jan;55(1):112-122
pubmed: 36510025
Annu Rev Genomics Hum Genet. 2014;15:151-71
pubmed: 24773320
Nucleic Acids Res. 1991 Aug 11;19(15):4293
pubmed: 1870982
Exp Mol Med. 2017 Apr 28;49(4):e322
pubmed: 28450738
Nat Genet. 2016 Feb;48(2):134-43
pubmed: 26691988
Sci Rep. 2021 Jun 23;11(1):13114
pubmed: 34162900
Gene. 1999 Sep 17;237(2):343-9
pubmed: 10521658
Trans Am Ophthalmol Soc. 2006;104:232-40
pubmed: 17471344
Cornea. 2009 Jun;28(5):524-9
pubmed: 19421045
Science. 2017 May 5;356(6337):
pubmed: 28473536
Nat Rev Mol Cell Biol. 2019 Oct;20(10):590-607
pubmed: 31399642
PLoS Genet. 2017 Mar 9;13(3):e1006646
pubmed: 28278150
BMC Cancer. 2022 Jun 21;22(1):685
pubmed: 35729618
Nat Genet. 2022 Jul;54(7):950-962
pubmed: 35710981
Am J Hum Genet. 2018 Nov 1;103(5):654-665
pubmed: 30401456
iScience. 2023 Apr 03;26(4):106417
pubmed: 37153444
Trends Genet. 2022 Mar;38(3):258-272
pubmed: 34535299
Bioinformatics. 2018 Aug 1;34(15):2538-2545
pubmed: 29579179
PLoS Genet. 2014 May 15;10(5):e1004383
pubmed: 24830394
Nat Genet. 2019 Apr;51(4):606-610
pubmed: 30742112
Cell. 2019 Mar 21;177(1):200-220
pubmed: 30901541
Proc Natl Acad Sci U S A. 2019 May 28;116(22):10883-10888
pubmed: 31076557
Nat Genet. 2021 Jan;53(1):110-119
pubmed: 33349701
Sci Rep. 2018 Dec 4;8(1):17605
pubmed: 30514905
Nat Commun. 2022 Oct 7;13(1):5827
pubmed: 36207300
Trends Genet. 2022 Jul;38(7):676-707
pubmed: 35504755
Nat Commun. 2018 Jan 15;9(1):224
pubmed: 29335400
J Hum Genet. 2020 Aug;65(8):657-665
pubmed: 32277175
Clin Epigenetics. 2019 Mar 14;11(1):49
pubmed: 30871624
Nat Genet. 2022 Jan;54(1):18-29
pubmed: 34980917
Nucleic Acids Res. 2014 Dec 1;42(21):
pubmed: 25294822
Science. 2020 Sep 11;369(6509):1318-1330
pubmed: 32913098
Nat Commun. 2018 Mar 2;9(1):918
pubmed: 29500431
Nat Rev Genet. 2012 Jan 04;13(2):97-109
pubmed: 22215131
Cell Rep. 2020 Jan 28;30(4):1246-1259.e6
pubmed: 31995762
Genome Biol. 2010;11(3):R25
pubmed: 20196867
Antioxidants (Basel). 2021 Apr 24;10(5):
pubmed: 33923192
Hum Reprod. 2019 May 1;34(5):804-812
pubmed: 30989213
Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3469-79
pubmed: 17652714
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Nat Genet. 2018 Jul;50(7):956-967
pubmed: 29955180
Open Med (Wars). 2016 Dec 22;11(1):578-583
pubmed: 28352849
Eye (Lond). 2001 Jun;15(Pt 3):376-83
pubmed: 11450761
Nat Genet. 2015 Nov;47(11):1228-35
pubmed: 26414678
Ophthalmology. 2017 Apr;124(4):479-487
pubmed: 28089680
Nat Commun. 2015 Feb 26;6:6326
pubmed: 25716334
PLoS Genet. 2020 Sep 1;16(9):e1008934
pubmed: 32870927
Nat Genet. 2022 Nov;54(11):1630-1639
pubmed: 36280734
PLoS One. 2016 Jun 20;11(6):e0157776
pubmed: 27322064
PLoS Genet. 2006 Dec;2(12):e190
pubmed: 17194218
Science. 2001 Feb 16;291(5507):1304-51
pubmed: 11181995
Science. 2018 Sep 28;361(6409):1336-1340
pubmed: 30262495
Cell. 2015 Aug 27;162(5):1039-50
pubmed: 26300124
Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2280-90
pubmed: 16723435
Exp Eye Res. 2015 Oct;139:22-36
pubmed: 26215528
Curr Protoc Bioinformatics. 2014 Sep 08;47:11.12.1-34
pubmed: 25199790
Nat Rev Genet. 2022 Oct;23(10):585-605
pubmed: 35501397
Atherosclerosis. 2001 Sep;158(1):227-31
pubmed: 11500195
Genom Data. 2016 May 26;9:22-4
pubmed: 27330998
Bioinformatics. 2017 Feb 15;33(4):558-560
pubmed: 28035024
Bioinformatics. 2016 May 15;32(10):1479-85
pubmed: 26708335
Int J Med Sci. 2018 Feb 12;15(5):430-435
pubmed: 29559831
Science. 2020 Sep 11;369(6509):
pubmed: 32913075
Am J Ophthalmol. 2007 Apr;143(4):607-15
pubmed: 17280640
Nat Neurosci. 2016 Jan;19(1):40-7
pubmed: 26619358
Front Bioinform. 2021 Apr 01;1:638255
pubmed: 36303779
Annu Rev Vis Sci. 2021 Sep 15;7:633-664
pubmed: 34061570
Invest Ophthalmol Vis Sci. 2016 Sep 1;57(11):4721-32
pubmed: 27607418
Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4484-90
pubmed: 15557458
Nat Rev Genet. 2019 Aug;20(8):437-455
pubmed: 31086298
Nat Genet. 2022 Sep;54(9):1345-1354
pubmed: 35995948
Am J Hum Genet. 2016 Dec 1;99(6):1245-1260
pubmed: 27866706
Nat Commun. 2017 May 18;8:15452
pubmed: 28516912
Nucleic Acids Res. 2017 Feb 28;45(4):e22
pubmed: 27924034
Am J Hum Genet. 2022 May 5;109(5):767-782
pubmed: 35452592