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10 APR, 2025
An international research team, led by Helmholtz Munich in collaboration with the Institute of Genetics and Cancer (IGC), has conducted the largest genome-wide association study (GWAS) on osteoarthritis to date. Analyzing genetic data from nearly two million individuals—including participants from the Generation Scotland cohort—the study aims to deepen understanding of osteoarthritis and uncover new drug targets.
Osteoarthritis is the leading cause of disability and chronic pain globally, with the number of affected individuals projected to reach one billion within 25 years. Despite its prevalence, there are currently no disease-modifying treatments. Advancing knowledge of both disease mechanisms and genetic contributors is essential to develop effective therapies.
GWAS involves scanning genomes to identify variants associated with specific conditions. In this study, researchers compared the genomes of 489,975 osteoarthritis patients with 1,472,094 controls, identifying 962 genetic variants linked to the disease—513 of which were previously unknown.
To translate these findings into biological insights, the team integrated the GWAS data with single-cell multi-omic profiles from developing skeletal tissue and functional multi-omic data—including genomic, transcriptomic, proteomic, and epigenomic analyses—from primary joint tissues. This approach identified 700 effector genes potentially mediating the link between genetic variants and disease development.
Eight biological processes were found to be enriched with these effector genes, offering insight into disease pathways. These included circadian rhythm regulation and developmental signaling.
Notably, around 10percentage of the identified genes encode proteins targeted by existing approved drugs, opening the door to potential drug repurposing opportunities for osteoarthritis.
Source: https://institute-genetics-cancer.ed.ac.uk/new-study-identifies-drug-targets-for-osteoarthritis