Pulse Brain · Growing Health Evidence Index
Tier 1 — Meta-analysis / systematic reviewPeer-reviewed

Translational genomics of osteoarthritis in 1,962,069 individuals

Konstantinos Hatzikotoulas, Lorraine Southam, Lilja Stefánsdóttir, Cindy G. Boer, Merry‐Lynn McDonald, J. Patrick Pett, Young‐Chan Park, Margo Tuerlings, Rick Mulders, Andrei Barysenka, Ana Luiza Arruda, Vinicius Tragante, Alison Rocco, Norbert Bittner, Shibo Chen, Susanne Horn, Vinodh Srinivasasainagendra, Ken To, Georgia Katsoula, Peter Kreitmaier, Amabel Tenghe, Arthur Gilly, Liubov Arbeeva, Lane G. Chen, Agathe de Pins, Daniel Dochtermann, Cecilie Henkel, Jonas Höijer, Shuji Ito, Penelope A. Lind, Bitota K Lukusa-Sawalena, Aye Ko Ko Minn, Marina Mola-Caminal, Akira Narita, Chelsea Nguyen, Ene Reimann, Micah Silberstein, Anne Heidi Skogholt, Hemant K. Tiwari, Michelle S. Yau, Ming Yue, Wei Zhao, Jin Zhou, George Alexiadis, Karina Banasik, Søren Brunak, Archie Campbell, Jackson T S Cheung, Joseph Dowsett, Tariq Faquih, Jessica D. Faul, Lijiang Fei, Anne Marie Fenstad, Takamitsu Funayama, Maiken E. Gabrielsen, Chinatsu Gocho, Kirill Gromov, Thomas Folkmann Hansen, Georgi Hudjashov, Þorvaldur Ingvarsson, Jessica Johnson, Helgi Jónsson, Saori Kakehi, Juha Karjalainen, Elisa Kasbohm, Susanna Lemmelä, Kuang Lin, Xiaoxi Liu, M. Loef, Massimo Mangino, Daniel L. McCartney, Iona Y. Millwood, Joshua Richman, Mary B. Roberts, Kathleen A. Ryan, Dino Samartzis, Manu Shivakumar, Søren Thorgaard Skou, Sachiyo Sugimoto, Ken Suzuki, Hiroshi Takuwa, Maris Teder‐Laving, Laurent F. Thomas, Kohei Tomizuka, Constance Turman, Stefan Weiß, Tian Wu, Eleni Zengini, Yanfei Zhang, George C. Babis, FinnGen, David A. van Heel, HUNT All-In Pain, Bendik Winsvold, Maiken Gabrielsen, Million Veteran Program, Manuel A. R. Ferreira, George C. Babis, Aris Baras, Tyler Barker

Nature · 2025

Read source ↗ All evidence

Summary

This large-scale translational genomics study integrated GWAS data from nearly 2 million participants to establish 962 genetic associations with osteoarthritis, identifying 513 previously unreported loci. By incorporating single-cell multiomics and multi-omics profiles of joint tissues, the research implicated 700 effector genes and converged on eight biological processes, including circadian regulation and multiple developmental signalling pathways. The findings suggest that rare coding variants have stronger effects than common variants and identify potential drug-repurposing candidates, offering translational pathways toward disease-modifying treatments for this rapidly growing health burden.

Regional applicability

These genomic findings are relevant to the United Kingdom's biomedical research infrastructure and NHS clinical practice, as osteoarthritis affects a substantial proportion of the UK population. The identification of drug-repurposing targets and biological pathways may inform future therapeutic development and personalised medicine approaches applicable to UK patient populations.

Key measures

Genome-wide association study signals; transcriptome, proteome and epigenome profiles of primary joint tissues; rare coding-variant burden associations; drug-repurposing opportunities (10% of effector genes targeted by approved drugs)

Outcomes reported

The study identified 962 independent genetic associations with osteoarthritis across nearly 2 million individuals, of which 513 were novel. The research implicated 700 effector genes and highlighted eight biological processes involved in disease pathogenesis, including circadian clock regulation, glial-cell processes, and multiple signalling pathways.

Theme
Nutrition & health
Subject
Dietary patterns & chronic disease
Study type
Meta-analysis
Study design
Meta-analysis
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/s41586-025-08771-z
Catalogue ID
SNmoj1yhqy-yr8uu8

Topic tags

Pulse AI · ask about this record

Dig deeper with Pulse AI.

Pulse AI has read the whole catalogue. Ask about this record, its theme, or how the findings apply to UK farming and policy — every answer cites the underlying studies.