Osteoarthritis is one of the leading causes of disability and pain worldwide, with over 300 million people affected (PMID: 30496104). As one of the most rapidly-rising conditions globally, the societal burden of osteoarthritis is enormous (PMID: 30496104, PMID: 24662640), and is accompanied by substantial multimorbidity (PMID: 28376838). Currently no curative treatments are available, and management strategies focus on symptom alleviation through pain relief and joint replacement surgery. A detailed understanding of disease etiopathology and novel drug targets are therefore urgently needed and eagerly anticipated.
Osteoarthritis is a complex degenerative disease of the whole joint, characterised by cartilage degeneration, subchondral bone thickening, osteophyte formation and synovial inflammation (PMID: 31034380). Risk for developing osteoarthritis and its major clinical symptom, joint pain, consists of a complex interplay between environmental factors and underlying genetic variation (PMID: 14698640). Osteoarthritis is one of the most common causes of chronic musculoskeletal pain, but the reason why people experience pain is not completely understood.
The applying group has ample experience in the field of (genetic) epidemiology of osteoarthritis and chronic pain and has contributed to much of the progress made in genetics of osteoarthritis, contributing to key advances in (genetic) epidemiology of osteoarthritis (PMID: 30715766, PMID: 29559693, PMID: 28855172). Recently, major advances were made in elucidating the genetic background of osteoarthritis, using genome-wide association studies (GWAS) (PMID: 29559693, PMID: 30374069, PMID: 30664745), mainly taking advantage of the UKBB study, establishing ± 50 risk single nucleotide variants (SNVs) to date. However, these loci only explain a small proportion of the phenotypic variance. In addition, the loci were identified in the UKBB-study and were not replicated in other populations, leaving the question open whether the identified genetic loci are robust across the Dutch population.
Recently, the genetics of osteoarthritis consortium (GO) was founded, which is a global collaboration with a focus on progressing our understanding of the genetic underpinning of osteoarthritis (https://www.genetics-osteoarthritis.com) The primary applicant of this proposal is co-leading this effort and we have managed to collaborate with many large biobanks across the world. The current proposal aims to analyse the genetic data of Lifelines on osteoarthritis outcomes and share summary statistics with the GO-consortium.