ArticleJournal of orthopaedic surgery and research2024
Identification of novel drug targets for osteoarthritis by integrating genetics and proteomes from blood.
Article in Journal of orthopaedic surgery and research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- IGF2BP3 Overexpression Accelerates Osteoarthritis Progression by Promoting Glycolysis via mThe Kaohsiung journal of medical sciences · 2026Article
- Deciphering the shared genetic structure between hip osteoarthritis and femoral neck bone mineral density.Frontiers in genetics · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
backgroundOsteoarthritis (OA) is a degenerative osteoarticular disease, involving genetic predisposition. How the risk variants confer the risk of OA through their effects on proteins remains largely unknown. Therefore, we aimed to discover new and effective drug targets for OA and its subtypes.
methodsA proteome-wide association study (PWAS) was performed based on OA and its subtypes genome-wide association studies (GWAS) summary datasets and the protein quantitative trait loci (pQTL) data. Subsequently, Mendelian randomization (MR) and colocalization analysis was conducted to estimate the associations between protein and OA risk. The replication analysis was performed in an independent dataset of human plasma pQTL data.
resultsThe abundance of seven proteins was causally related to OA, two proteins to knee OA and six proteins to hip OA, respectively. We replicated 2 of these proteins using an independent pQTL dataset. With the further support of colocalization, and higher ECM1 level was causally associated with a higher risk of OA and hip OA. Higher PCSK1 level was causally associated with a lower risk of OA. And higher levels of ITIH1, EFEMP1, and ERLEC1 were associated with decreased risk of hip OA.
conclusionOur study provides new insights into the genetic component of protein abundance in OA and a promising therapeutic target for future drug development.
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