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Meta-analysis of Icelandic and UK data sets identifies missense variants in SMO, IL11, COL11A1 and 13 more new loci associated with osteoarthritis
- Source :
- Nature Genetics. 50:1681-1687
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
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.
- Subjects :
- 030203 arthritis & rheumatology
0301 basic medicine
medicine.medical_specialty
Case-control study
Genome-wide association study
Odds ratio
Osteoarthritis
Biology
medicine.disease
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Meta-analysis
Internal medicine
Genotype
Genetics
medicine
Missense mutation
Allele frequency
Subjects
Details
- ISSN :
- 15461718 and 10614036
- Volume :
- 50
- Database :
- OpenAIRE
- Journal :
- Nature Genetics
- Accession number :
- edsair.doi...........7ace5895ef6663ab11fb71ebef351cc8