Meta-analysis of Icelandic and UK data sets identifies missense variants in SMO, IL11, COL11A1 and 13 more new loci associated ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-12

AUTHORS

Unnur Styrkarsdottir, Sigrun H. Lund, Gudmar Thorleifsson, Florian Zink, Olafur A. Stefansson, Jon K. Sigurdsson, Kristinn Juliusson, Kristbjörg Bjarnadottir, Sara Sigurbjornsdottir, Stefan Jonsson, Kristjan Norland, Lilja Stefansdottir, Asgeir Sigurdsson, Gardar Sveinbjornsson, Asmundur Oddsson, Gyda Bjornsdottir, Reynir L. Gudmundsson, Gisli H. Halldorsson, Thorunn Rafnar, Ingileif Jonsdottir, Eirikur Steingrimsson, Gudmundur L. Norddahl, Gisli Masson, Patrick Sulem, Helgi Jonsson, Thorvaldur Ingvarsson, Daniel F. Gudbjartsson, Unnur Thorsteinsdottir, Kari Stefansson

ABSTRACT

Osteoarthritis has a highly negative impact on quality of life because of the associated pain and loss of joint function. Here we describe the largest meta-analysis so far of osteoarthritis of the hip and the knee in samples from Iceland and the UK Biobank (including 17,151 hip osteoarthritis patients, 23,877 knee osteoarthritis patients, and more than 562,000 controls). We found 23 independent associations at 22 loci in the additive meta-analyses, of which 16 of the loci were novel: 12 for hip and 4 for knee osteoarthritis. Two associations are between rare or low-frequency missense variants and hip osteoarthritis, affecting the genes SMO (rs143083812, frequency 0.11%, odds ratio (OR) = 2.8, P = 7.9 × 10-12, p.Arg173Cys) and IL11 (rs4252548, frequency 2.08%, OR = 1.30, P = 2.1 × 10-11, p.Arg112His). A common missense variant in the COL11A1 gene also associates with hip osteoarthritis (rs3753841, frequency 61%, P = 5.2 × 10-10, OR = 1.08, p.Pro1284Leu). In addition, using a recessive model, we confirm an association between hip osteoarthritis and a variant of CHADL1 (rs117018441, P = 1.8 × 10-25, OR = 5.9). Furthermore, we observe a complex relationship between height and risk of osteoarthritis. More... »

PAGES

1681-1687

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-018-0247-0

    DOI

    http://dx.doi.org/10.1038/s41588-018-0247-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1107733488

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30374069


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