TY - JOUR 
A1 - Evangelou, Evangelos
AU - Kerkhof, Hanneke J.M
AU - Styrkarsdottir, Unnur
AU - Ntzani, Evangelia E
AU - Bos, Steffan D
AU - Esko, Tonu
AU - Evans, Daniel S
AU - Metrustry, Sarah
AU - Panoutsopoulou, Kalliope
AU - Ramos, Yolande F M
AU - Thorleifsson, Gudmar
AU - Tsilidis, Konstantinos K
AU - Arden, Nigel
AU - Aslam, Nadim
AU - Bellamy, Nicholas
AU - Birrell, Fraser
AU - BLANCO GARCIA, FRANCISCO JAVIER
AU - Carr, Andrew
AU - Chapman, Kay
AU - Day-Williams, Aaron G
AU - Deloukas, Panos
AU - Doherty, Michael
AU - Engström, Gunnar
AU - Helgadottir, Hafdis T
AU - Hofman, Albert
AU - Ingvarsson, Thorvaldur
AU - Jonsson, Helgi
AU - Keis, Aime
AU - Keurentjes, J Christiaan
AU - Kloppenburg, Margreet
AU - Lind, Penelope A
AU - McCaskie, Andrew
AU - Martin, Nicholas G
AU - Milani, Lili
AU - Montgomery, Grant W
AU - Nelissen, Rob G H H
AU - Nevitt, Michael C
AU - Nilsson, Peter M
AU - Ollier, William Er
AU - Parimi, Neeta
AU - Rai, Ashok
AU - Ralston, Stuart H
AU - Reed, Mike R
AU - Riancho, Jose A
AU - Rivadeneira, Fernando
AU - Rodríguez Fontenla, Cristina
AU - Southam, Lorraine
AU - Thorsteinsdottir, Unnur
AU - Tsezou, Aspasia
AU - Wallis, Gillian A
AU - Wilkinson, J Mark
AU - González Martínez-Pedrayo, Antonio
AU - Lane, Nancy E
AU - Lohmander, L Stefan
AU - Loughlin, John
AU - Metspalu, Andres
AU - Uitterlinden, Andre G
AU - Jonsdottir, Ingileif
AU - Stefansson, Kari
AU - Slagboom, P Eline
AU - Zeggini, Eleftheria
AU - Meulenbelt, Ingrid
AU - Ioannidis, John Pa
AU - Spector, Tim D
AU - van Meurs, Joyce B J
AU - Valdes, Ana M
T1 - A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
Y1 - 2014
SN - 0003-4967
UR - http://hdl.handle.net/20.500.11940/4576
AB - 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.
KW - Osteoarthritis, Hip
KW - Gene Frequency
KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2
KW - European Continental Ancestry Group
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Osteoartritis de la Cadera
KW - Frecuencia de los Genes
KW - Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina
KW - Grupo de Ascendencia Continental Europea
KW - Predisposición Genética a la Enfermedad
KW - Estudio de Asociación del Genoma Completo
LA - eng
ER -