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Lookup NU author(s): Dr Sarah RiceORCiD, Kat Cheung, Professor John LoughlinORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Background Despite recent advances in the understanding of the genetic architecture of osteoarthritis (OA), only two genetic loci have been identified for OA of the hand, in part explained by the complexity of the different hand joints and heterogeneity of OA pathology.Methods We used data from the Rotterdam Study (RSI, RSII and RSIII) to create three hand OA phenotypes based on clustering patterns of radiographic OA severity to increase power in our modest discovery genome-wide association studies in the RS (n=8700), and sought replication in an independent cohort, the Framingham Heart Study (n=1203). We used multiple approaches that leverage different levels of information and functional data to further investigate the underlying biological mechanisms and candidate genes for replicated loci. We also attempted to replicate known OA loci at other joint sites, including the hips and knees.Results We found two novel genome-wide significant loci for OA in the thumb joints. We identified WNT9A as a possible novel causal gene involved in OA pathogenesis. Furthermore, several previously identified genetic loci for OA seem to confer risk for OA across multiple joints: TGFa, RUNX2, COL27A1, ASTN2, IL11 and GDF5 loci.Conclusions We identified a robust novel genetic locus for hand OA on chromosome 1, of which WNT9A is the most likely causal gene. In addition, multiple genetic loci were identified to be associated with OA across multiple joints. Our study confirms the potential for novel insight into the genetic architecture of OA by using biologically meaningful stratified phenotypes.
Author(s): Boer CG, Yau MS, Rice SJ, Coutinho de Almeida R, Cheung K, Styrkarsdottir U, Southam L, Broer L, Wilkinson JM, Uitterlinden AG, Zeggini E, Felson D, Loughlin J, Young M, Capellini TD, Meulenbelt I, van Meurs JBJ
Publication type: Article
Publication status: Published
Journal: Annals of the Rheumatic Diseases
Year: 2021
Volume: 80
Issue: 3
Pages: 367-375
Print publication date: 11/02/2021
Online publication date: 14/10/2020
Acceptance date: 08/09/2020
Date deposited: 27/10/2020
ISSN (print): 0003-4967
ISSN (electronic): 1468-2060
Publisher: BMJ Publishing Group
URL: https://doi.org/10.1136/annrheumdis-2020-217834
DOI: 10.1136/annrheumdis-2020-217834
PubMed id: 33055079
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