Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression.
Australia
Case-Control Studies
Cytoskeletal Proteins
/ genetics
Disease Progression
Eye Proteins
/ genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Glaucoma
/ etiology
Glycoproteins
/ genetics
Humans
Intraocular Pressure
/ genetics
Multifactorial Inheritance
Odds Ratio
Optic Nerve
/ physiology
Penetrance
Polymorphism, Single Nucleotide
Trabeculectomy
/ adverse effects
United Kingdom
United States
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
24
05
2019
accepted:
21
11
2019
pubmed:
22
1
2020
medline:
14
4
2020
entrez:
22
1
2020
Statut:
ppublish
Résumé
Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 × 10
Identifiants
pubmed: 31959993
doi: 10.1038/s41588-019-0556-y
pii: 10.1038/s41588-019-0556-y
pmc: PMC8056672
mid: NIHMS1685412
doi:
Substances chimiques
Cytoskeletal Proteins
0
Eye Proteins
0
Glycoproteins
0
trabecular meshwork-induced glucocorticoid response protein
0
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
160-166Subventions
Organisme : Medical Research Council
ID : MC_PC_12028
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : U01 HG004728
Pays : United States
Organisme : NEI NIH HHS
ID : R21 EY028671
Pays : United States
Organisme : Medical Research Council
ID : MR/T040912/1
Pays : United Kingdom
Organisme : NEI NIH HHS
ID : R01 EY022305
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY015473
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : NEI NIH HHS
ID : P30 EY031631
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
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