A large-scale genome-wide association study (GWAS) has revealed potential therapeutic targets for osteoarthritis.

Osteoarthritis, which is caused by the breakdown of cartilage in joints, is the third most rapidly growing health condition causing disability and is predicted to affect one billion people worldwide by 2050. An international team of researchers, led by Helmholtz Munich, Germany, has conducted the largest ever GWAS into osteoarthritis by analysing nearly two million genomes, revealing 962 genetic loci with a significant link to the condition. More than 500 of these associations have never previously been identified, providing new insights into osteoarthritis development.

'Genetic variants associated with osteoarthritis risk are widespread across osteoarthritis patients,' said Dr Konstantinos Hatzikotoulas, from the Institute of Translational Genomics at Helmholtz Munich and co-first author of the study, published in Nature. 'Our newly gained knowledge about them can enable improved patient selection for clinical trials and personalised medicine approaches.'

GWAS's aim to identify genetic loci that increase a person's risk of developing a disease by comparing the genomes of patients to the genomes of those without the condition. This study has revealed 700 genes likely to be involved in osteoarthritis, most of which are involved in eight key signalling pathways known to be linked to the disease. An example is the ALDH1A2 gene involved in the retinoic acid signalling pathway, which showed the strongest association with osteoarthritis in this study.

'What we found in the largest osteoarthritis GWAS study not only advances our understanding of the disease but also lays the groundwork for developing more effective and personalised therapies that could transform osteoarthritis care', said Professor Eleftheria Zeggini, director of the Institute of Translational Genomics at Helmholtz Munich, who led the study.

Currently, no therapies exist for osteoarthritis that delay or reverse disease progression, with interventions limited to pain management or joint replacement. Previous research suggests that developing new drugs to target cartilage stem cells could be used as a treatment (see BioNews 1215), however this new study indicates existing drugs could also be repurposed to treat the condition. Ten percent of genes identified as linked to osteoarthritis in this study encode proteins targeted by existing therapies, suggesting treatments could be tailored to patients depending on their genetic variants.

While these findings show promise for providing patients with new treatment avenues in the future, functional analyses of these genes and biological modelling are still needed to determine the role these variants play in osteoarthritis development. Further work is also needed to identify genetic risk factors for osteoarthritis in people of non-European descent, as 87 percent of genomes analysed in this study came from individuals of European ancestry.