Pulse Brain · Growing Health Evidence Index
Peer-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

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Summary

. As no disease-modifying treatments exist for osteoarthritis, a better understanding of disease aetiopathology is urgently needed. Here we perform a genome-wide association study meta-analyses across up to 489,975 cases and 1,472,094 controls, establishing 962 independent associations, 513 of which have not been previously reported. Using single-cell multiomics data, we identify signal enrichment in embryonic skeletal development pathways. We integrate orthogonal lines of evidence, including transcriptome, proteome and epigenome profiles of primary joint tissues, and implicate 700 effector genes. Within these, we find rare coding-variant burden associations with effect sizes that are consistently higher than common frequency variant associations. We highlight eight biological processes in

Source type
Peer-reviewed study
DOI
10.1038/s41586-025-08771-z
Catalogue ID
SNmoj1yhqy-yr8uu8
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