Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

TLDR

Osteoarthritis affects over 300 million people worldwide. The study performs a GWAS meta‑analysis of 826,690 individuals, uncovering 100 independent risk variants across 11 osteoarthritis phenotypes, including 52 novel loci. The authors integrate functional genomics data from primary patient tissues—articular cartilage, subchondral bone, and osteophytic cartilage—to pinpoint high‑confidence effector genes. The analysis identifies joint‑specific, sex‑specific, and early‑onset risk loci, links OA genetics to pain and neuronal pathways, and highlights key molecular players and drug targets.

Abstract

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.