A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
Author(s)
Type
Journal Article
Abstract
OBJECTIVES: Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. METHODS: We performed a two-stage meta-analysis on more than 78,000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. RESULTS: We accumulated 11,277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10(-8)) and follow-up studies (p=7.3×10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10(-6), OR=1.27 in male specific analysis). CONCLUSIONS: Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
Date Issued
2013-08-29
Date Acceptance
2013-07-26
Citation
Annals of the Rheumatic Diseases, 2013, 73 (12), pp.2130-2136
ISSN
1468-2060
Publisher
BMJ Publishing Group
Start Page
2130
End Page
2136
Journal / Book Title
Annals of the Rheumatic Diseases
Volume
73
Issue
12
Copyright Statement
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/
Subjects
Epidemiology
Gene Polymorphism
Osteoarthritis
Calcium-Calmodulin-Dependent Protein Kinase Type 2
European Continental Ancestry Group
Female
Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study
HMGN Proteins
Homeodomain Proteins
Humans
Immediate-Early Proteins
Male
Nuclear Receptor Coactivator 3
Osteoarthritis, Hip
Polymorphism, Single Nucleotide
Protein-Serine-Threonine Kinases
Protein-Tyrosine Kinases
Sex Factors
arcOGEN Consortium
Arthritis & Rheumatology
1103 Clinical Sciences
1107 Immunology
1117 Public Health And Health Services
Publication Status
Published