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Nat Genet. 2018 Dec;50(12):1681-1687. doi: 10.1038/s41588-018-0247-0. Epub 2018 Oct 29.

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

Author information

1
deCODE genetics/Amgen, Inc., Reykjavik, Iceland. unnur.styrkarsdottir@decode.is.
2
deCODE genetics/Amgen, Inc., Reykjavik, Iceland.
3
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
4
Biochemistry and Molecular Biology, BioMedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
5
Department of Immunology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland.
6
Department of Medicine, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland.
7
Department of Orthopedic Surgery, Akureyri Hospital, Akureyri, Iceland.
8
Institution of Health Science, University of Akureyri, Akureyri, Iceland.
9
School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
10
deCODE genetics/Amgen, Inc., Reykjavik, Iceland. kstefans@decode.is.
11
Faculty of Medicine, University of Iceland, Reykjavik, Iceland. kstefans@decode.is.

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.

PMID:
30374069
DOI:
10.1038/s41588-018-0247-0

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