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Lookup NU author(s): Jack Roberts, Dr Sarah RiceORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024.Purpose of Review: Osteoarthritis is a complex and highly polygenic disease. Over 100 reported osteoarthritis risk variants fall in non-coding regions of the genome, ostensibly conferring functional effects through the disruption of regulatory elements impacting target gene expression. In this review, we summarise the progress that has advanced our knowledge of gene enhancers both within the field of osteoarthritis and more broadly in complex diseases. Recent Findings: Advances in technologies such as ATAC-seq have facilitated our understanding of chromatin states in specific cell types, bolstering the interpretation of GWAS and the identification of effector genes. Their application to osteoarthritis research has revealed enhancers as the principal regulatory element driving disease-associated changes in gene expression. However, tissue-specific effects in gene regulatory mechanisms can contribute added complexity to biological interpretation. Summary: Understanding gene enhancers and their altered activity in specific cell and tissue types is the key to unlocking the genetic complexity of osteoarthritis. The use of single-cell technologies in osteoarthritis research is still in its infancy. However, such tools offer great promise in improving our functional interpretation of osteoarthritis GWAS and the identification of druggable targets. Large-scale collaborative efforts will be imperative to understand tissue and cell-type specific molecular mechanisms underlying enhancer function in disease.
Author(s): Roberts JB, Rice SJ
Publication type: Review
Publication status: Published
Journal: Current Rheumatology Reports
Year: 2024
Volume: 26
Pages: 222–234
Online publication date: 02/03/2024
Acceptance date: 07/02/2024
ISSN (print): 1523-3774
ISSN (electronic): 1534-6307
Publisher: Springer
URL: https://doi.org/10.1007/s11926-024-01142-z
DOI: 10.1007/s11926-024-01142-z
PubMed id: 38430365
