Cindy Boer

160 | Chapter 4.1 Abstract Osteoarthritis is the most prevalent musculoskeletal disease with over 300 million people affected worldwide. Here, we conduct a genome-wide association study me- ta-analysis for osteoarthritis across 826,690 individuals, and identify 55 newly associ- ated risk variants, including 3 female-specific signals, bringing the total number to 148. We identify the first thumb and spine osteoarthritis risk variants, sex-specific risk loci, and differences between weight-bearing and non-weight bearing joints. By integrating functional genomics data from primary patient tissues, we identify likely causal genes for osteoarthritis loci. We find strong evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify circulating protein levels that are on the causal path for osteoarthritis. Our results provide new insights into disease aetiopathogenesis and highlight attractive drug targets to accelerate translation.