The genetic architecture of osteoarthritis: insights from UK Biobank

Eleni Zengini; Konstantinos Hatzikotoulas; Ioanna Tachmazidou; Julia Steinberg; Fernando Pires Hartwig; Lorraine Southam; Sophie Hackinger; Cindy Germaine Boer; Unnur Styrkársdóttir; Arthur Gilly; Dániel Süveges; Britt Kilian; Þorvaldur Ingvarsson; Helgi Jónsson; George C. Babis; Andrew W. McCaskie; André Gerardus Uitterlinden; Joyce B. J. van Meurs; Unnur Þorsteinsdóttir; Kāri Stefánsson; George Davey Smith; Jeremy Mark Wilkinson; Eleftheria Zeggini

doi:10.1038/s41588-018-0079-y

GeneticsNature GeneticsMar 20, 2018

Peer-reviewed journal article

The genetic architecture of osteoarthritis: insights from UK Biobank

Eleni Zengini, Konstantinos Hatzikotoulas iD, Ioanna Tachmazidou iD, Julia Steinberg iD, Fernando Pires Hartwig iD, Lorraine Southam iD, Sophie Hackinger iD, Cindy Germaine Boer iD, Unnur Styrkársdóttir iD, Arthur Gilly iD, Dániel Süveges iD, Britt Kilian iD, Þorvaldur Ingvarsson, Helgi Jónsson iD, George C. Babis iD, Andrew W. McCaskie iD, André Gerardus Uitterlinden iD, Joyce B. J. van Meurs iD, Unnur Þorsteinsdóttir iD, Kāri Stefánsson iD, George Davey Smith iD, Jeremy Mark Wilkinson iD, Eleftheria Zeggini iD

Abstract

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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