Combining functional genomics with the largest ever genome-wide association study of osteoarthritis has identified disease-linked variants and new drug targets. An international research team, led by Helmholtz Munich and including researchers from the Institute of Genetics and Cancer (IGC), has carried out the largest ever genome-wide association study (GWAS) on osteoarthritis using the genetic information of nearly two million people - including those from the Generation Scotland cohort - to better understand the condition and identify new drug targets. Osteoarthritis is the leading cause of disability and chronic pain worldwide, with the total number of patients estimated to reach one billion in the next 25 years. Despite this, no disease-modifying treatments are currently available for osteoarthritis patients. Greater understanding of both the mechanism of the disease, and the genetic components underlying it, will be needed to develop treatments. Genome-wide association studies examine genetic differences across the genome and can be used to highlight genetic sequences associated with conditions or traits. The research team compared the genetic sequences of 489,975 individuals with osteoarthritis with 1,472,094 people without the condition to identify 962 genetic variations more commonly found in those with osteoarthritis, 513 of which had not previously been identified. The findings of the GWAS were then combined with single-cell multi-omic data from the developing skeleton, and functional multi-omic data (genomics, transcriptomic, proteomic, epigenomic) from primary joint tissues, to implicate 700 effector genes that could mediate the relationship between disease-associated genetic variation and disease. Eight biological processes were identified that were enriched for effector genes, shedding light on the biological mechanism of the disease. These include both the circadian clock and development signalling pathways. The study found that 10% of the genes identified express a protein that is a known target of already approved drugs, which potentially could be repurposed for new osteoarthritis treatments. These findings were published in a paper entitled ‘Translational genomics of osteoarthritis in 1,962,069 individuals’ in the journal Nature. This study included genetic data from over 20,000 Generation Scotland volunteers with electronic health record information available on nine tissue-specific subtypes of osteoarthritis. Combined with data from the many other studies, this created a rich data source to explore the genetic sequences associated with this disease. This massive international study has greatly advanced the understanding of genes underlying degenerative joint disease and identified potential new therapies. Emeritus Professor Caroline Hayward Institute of Genetics and Cancer What we have 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. Professor Eleftheria Zeggini Director of the Institute of Translational Genomics at Helmholtz Munich [Image credit – SeizaVisuals via Getty Images] Read the full study (external link) Generation Scotland Emeritus Professor Caroline Hayward Tags 2025 Publication date 10 Apr, 2025
