A proteogenomic signature of age-related macular degeneration in blood.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 06 2022
13 06 2022
Historique:
received:
06
08
2021
accepted:
01
06
2022
entrez:
13
6
2022
pubmed:
14
6
2022
medline:
16
6
2022
Statut:
epublish
Résumé
Age-related macular degeneration (AMD) is one of the most common causes of visual impairment in the elderly, with a complex and still poorly understood etiology. Whole-genome association studies have discovered 34 genomic regions associated with AMD. However, the genes and cognate proteins that mediate the risk, are largely unknown. In the current study, we integrate levels of 4782 human serum proteins with all genetic risk loci for AMD in a large population-based study of the elderly, revealing many proteins and pathways linked to the disease. Serum proteins are also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study identifies several proteins that are causally related to the disease and are directionally consistent with the observational estimates. In this work, we present a robust and unique framework for elucidating the pathobiology of AMD.
Identifiants
pubmed: 35697682
doi: 10.1038/s41467-022-31085-x
pii: 10.1038/s41467-022-31085-x
pmc: PMC9192739
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3401Subventions
Organisme : NIA NIH HHS
ID : N01AG12100
Pays : United States
Organisme : NIDA NIH HHS
ID : HHSN271201200022C
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA EY000401
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG065596
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
Nat Commun. 2022 Jan 25;13(1):480
pubmed: 35078996
Redox Biol. 2017 Oct;13:255-265
pubmed: 28600982
Theranostics. 2019 Jan 30;9(4):1170-1180
pubmed: 30867823
J Proteome Res. 2017 Dec 1;16(12):4299-4310
pubmed: 28938075
Nat Commun. 2019 Jul 4;10(1):2961
pubmed: 31273197
Ophthalmology. 2013 Sep;120(9):1880-92
pubmed: 23523162
Eur J Med Genet. 2013 Feb;56(2):72-9
pubmed: 23103884
Am J Hum Genet. 2021 Aug 5;108(8):1385-1400
pubmed: 34260948
Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3356-63
pubmed: 17591909
PLoS One. 2017 May 18;12(5):e0177749
pubmed: 28542375
J Biol Chem. 2019 Feb 8;294(6):1944-1955
pubmed: 30530495
Nature. 2008 Mar 27;452(7186):423-8
pubmed: 18344981
J Biol Chem. 2007 Jun 8;282(23):16917-23
pubmed: 17439947
Sci Rep. 2018 Apr 3;8(1):5531
pubmed: 29615742
Proc Natl Acad Sci U S A. 2020 May 5;117(18):9942-9951
pubmed: 32321835
Genet Epidemiol. 2016 May;40(4):304-14
pubmed: 27061298
J Biol Chem. 2019 Aug 16;294(33):12432-12443
pubmed: 31248988
Science. 2005 Apr 15;308(5720):419-21
pubmed: 15761120
Ophthalmology. 2018 Jun;125(6):842-849
pubmed: 29366564
Nat Genet. 2006 Oct;38(10):1173-7
pubmed: 16998489
Proc Natl Acad Sci U S A. 2005 May 17;102(20):7227-32
pubmed: 15870199
Mol Immunol. 2007 Jul;44(13):3398-406
pubmed: 17399790
J Immunol. 2018 Apr 1;200(7):2280-2290
pubmed: 29483359
Science. 2005 Apr 15;308(5720):385-9
pubmed: 15761122
J Stat Softw. 2010;33(1):1-22
pubmed: 20808728
Neurobiol Aging. 2006 Jul;27(7):983-93
pubmed: 15979212
PLoS Genet. 2021 Sep 29;17(9):e1009440
pubmed: 34587156
Nature. 2018 Jun;558(7708):73-79
pubmed: 29875488
Nat Genet. 2016 Feb;48(2):134-43
pubmed: 26691988
Invest Ophthalmol Vis Sci. 2020 Mar 9;61(3):18
pubmed: 32176267
Proteomics. 2020 Jun;20(12):e1900278
pubmed: 32386347
Nat Genet. 2011 Oct 23;43(12):1232-6
pubmed: 22019782
Biochim Biophys Acta. 2008 Sep;1780(9):1062-9
pubmed: 18573314
Nat Med. 2019 Dec;25(12):1843-1850
pubmed: 31806903
Nat Med. 2019 Dec;25(12):1815-1816
pubmed: 31806904
Ophthalmology. 2016 Sep;123(9):1874-8
pubmed: 27378016
Transl Vis Sci Technol. 2019 Jan 25;8(1):14
pubmed: 30697465
J Clin Invest. 2011 Jan;121(1):369-83
pubmed: 21135502
Nature. 2008 Mar 27;452(7186):429-35
pubmed: 18344982
Arch Ophthalmol. 2007 Sep;125(9):1235-40
pubmed: 17846364
Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2966-74
pubmed: 19151382
Ophthalmology. 2018 Feb;125(2):245-254
pubmed: 28916333
PLoS Genet. 2014 May 15;10(5):e1004383
pubmed: 24830394
Science. 2020 Sep 11;369(6509):1318-1330
pubmed: 32913098
Prog Retin Eye Res. 2019 Mar;69:57-79
pubmed: 30423446
Metabolites. 2019 Jul 02;9(7):
pubmed: 31269701
Nat Genet. 2018 Mar;50(3):401-413
pubmed: 29507422
Int J Epidemiol. 2015 Apr;44(2):512-25
pubmed: 26050253
Trends Mol Med. 2021 Jan;27(1):20-30
pubmed: 32988739
PLoS One. 2010 Dec 07;5(12):e15004
pubmed: 21165148
Nat Commun. 2020 Feb 7;11(1):778
pubmed: 32034129
Science. 2018 Aug 24;361(6404):769-773
pubmed: 30072576
Ophthalmology. 2013 Nov;120(11):2292-9
pubmed: 23642856
Am J Hum Genet. 2021 Aug 5;108(8):1367-1384
pubmed: 34260947
Nat Commun. 2022 Jan 25;13(1):481
pubmed: 35079000
Ophthalmol Retina. 2021 Sep;5(9):855-867
pubmed: 33348085
Proc Natl Acad Sci U S A. 2019 Nov 26;116(48):24100-24107
pubmed: 31712411
Ophthalmology. 2014 Sep;121(9):1766-72
pubmed: 24768241
Nat Med. 2019 Dec;25(12):1851-1857
pubmed: 31792462
Am J Epidemiol. 2007 May 1;165(9):1076-87
pubmed: 17351290
J Proteome Res. 2009 Jan;8(1):113-7
pubmed: 19072545
PLoS One. 2013;8(1):e53830
pubmed: 23326517
Stat Med. 2016 May 20;35(11):1880-906
pubmed: 26661904
Cell. 2016 Aug 11;166(4):802-821
pubmed: 27518560
FASEB J. 2020 Sep;34(9):12502-12520
pubmed: 32721041
Lancet Glob Health. 2014 Feb;2(2):e106-16
pubmed: 25104651
Science. 2009 Oct 2;326(5949):140-4
pubmed: 19797661
Ophthalmology. 2013 Oct;120(10):2042-50
pubmed: 23706948
Science. 2005 Apr 15;308(5720):421-4
pubmed: 15761121
Hum Mol Genet. 2016 Aug 1;25(15):3143-3151
pubmed: 27270414
Nature. 2009 Sep 10;461(7261):218-23
pubmed: 19741703
Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7153-8
pubmed: 26039989
Science. 2016 Apr 1;352(6281):54-61
pubmed: 26917594
Cell. 2013 Apr 25;153(3):707-20
pubmed: 23622250
Invest Ophthalmol Vis Sci. 2011 Jul 29;52(8):5749-57
pubmed: 21508099
Invest Ophthalmol Vis Sci. 2008 Jul;49(7):2848-55
pubmed: 18344451
EMBO Mol Med. 2019 Nov 7;11(11):e10427
pubmed: 31566909
Transl Vis Sci Technol. 2020 Sep 11;9(10):12
pubmed: 32974084
Cell Metab. 2017 Nov 7;26(5):719-737.e6
pubmed: 28965825