Genetics of osteoarthritis.
DNA methylation
Epigenetics
Functional analysis
GWAS
Genetics
SNPs
Journal
Osteoarthritis and cartilage
ISSN: 1522-9653
Titre abrégé: Osteoarthritis Cartilage
Pays: England
ID NLM: 9305697
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
11
12
2020
revised:
17
02
2021
accepted:
06
03
2021
pubmed:
17
3
2021
medline:
27
4
2022
entrez:
16
3
2021
Statut:
ppublish
Résumé
Osteoarthritis genetics has been transformed in the past decade through the application of large-scale genome-wide association scans. So far, over 100 polymorphic DNA variants have been associated with this common and complex disease. These genetic risk variants account for over 20% of osteoarthritis heritability and the vast majority map to non-protein coding regions of the genome where they are presumed to act by regulating the expression of target genes. Statistical fine mapping, in silico analyses of genomics data, and laboratory-based functional studies have enabled the identification of some of these targets, which encode proteins with diverse roles, including extracellular signaling molecules, intracellular enzymes, transcription factors, and cytoskeletal proteins. A large number of the risk variants correlate with epigenetic factors, in particular cartilage DNA methylation changes in cis, implying that epigenetics may be a conduit through which genetic effects on gene expression are mediated. Some of the variants also appear to have been selected as humans adapted to bipedalism, suggesting that a proportion of osteoarthritis genetic susceptibility results from antagonistic pleiotropy, with risk variants having a positive role in joint formation but a negative role in the long-term health of the joint. Although data from an osteoarthritis genetic study has not yet directly led to a novel treatment, some of the osteoarthritis associated genes code for proteins that have available therapeutics. Genetic investigations are therefore revealing fascinating fundamental insights into osteoarthritis and can expose options for translational intervention.
Identifiants
pubmed: 33722698
pii: S1063-4584(21)00632-4
doi: 10.1016/j.joca.2021.03.002
pmc: PMC9067452
pii:
doi:
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
636-649Subventions
Organisme : Versus Arthritis
ID : 20771
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P020941/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R502182/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : JXR 10641
Pays : United Kingdom
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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