The genetic architecture of osteoarthritis: insights from UK Biobank
By
Eleni Zengini,
Konstantinos Hatzikotoulas,
Ioanna Tachmazidou,
Julia Steinberg,
Fernando P. Hartwig,
Lorraine Southam,
Sophie Hackinger,
Cindy G Boer,
Unnur Styrkarsdottir,
Daniel Suveges,
Britt Killian,
Arthur Gilly,
Thorvaldur Ingvarsson,
Helgi Jonsson,
George C. Babis,
Andrew McCaskie,
Andre G Uitterlinden,
Joyce B. J. van Meurs,
Unnur Thorsteinsdottir,
Kari Stefansson,
George Davey Smith,
Mark J. Wilkinson,
Eleftheria Zeggini
Posted 11 Aug 2017
bioRxiv DOI: 10.1101/174755
(published DOI: 10.1038/s41588-018-0079-y)
Osteoarthritis is a common complex disease with huge public health burden. Here we perform a genome-wide association study for osteoarthritis using data across 16.5 million variants from the UK Biobank resource. Following replication and meta-analysis in up to 30,727 cases and 297,191 controls, we report 9 new osteoarthritis loci, in all of which the most likely causal variant is non-coding. For three loci, we detect association with biologically-relevant radiographic endophenotypes, and in five signals we identify genes that are differentially expressed in degraded compared to intact articular cartilage from osteoarthritis patients. We establish causal effects for higher body mass index, but not for triglyceride levels or type 2 diabetes liability, on osteoarthritis.
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