RT Journal Article
SR Electronic
T1 The genetic architecture of osteoarthritis: insights from UK Biobank
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 174755
DO 10.1101/174755
A1 Eleni Zengini
A1 Konstantinos Hatzikotoulas
A1 Ioanna Tachmazidou
A1 Julia Steinberg
A1 Fernando P. Hartwig
A1 Lorraine Southam
A1 Sophie Hackinger
A1 Cindy G. Boer
A1 Unnur Styrkarsdottir
A1 Daniel Suveges
A1 Britt Killian
A1 Arthur Gilly
A1 Thorvaldur Ingvarsson
A1 Helgi Jonsson
A1 George C. Babis
A1 Andrew McCaskie
A1 Andre G. Uitterlinden
A1 Joyce B. J. van Meurs
A1 Unnur Thorsteinsdottir
A1 Kari Stefansson
A1 George Davey Smith
A1 Mark J. Wilkinson
A1 Eleftheria Zeggini
YR 2017
UL http://biorxiv.org/content/early/2017/08/11/174755.abstract
AB 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.