A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22.

Arthritis and Rheumatism
Hanneke J M KerkhofJoyce B van Meurs

Abstract

To identify novel genes involved in osteoarthritis (OA), by means of a genome-wide association study. We tested 500,510 single-nucleotide polymorphisms (SNPs) in 1,341 Dutch Caucasian OA cases and 3,496 Dutch Caucasian controls. SNPs associated with at least 2 OA phenotypes were analyzed in 14,938 OA cases and approximately 39,000 controls. Meta-analyses were performed using the program Comprehensive Meta-analysis, with P values <1 x 10(-7) considered genome-wide significant. The C allele of rs3815148 on chromosome 7q22 (minor allele frequency 23%; intron 12 of the COG5 gene) was associated with a 1.14-fold increased risk (95% confidence interval 1.09-1.19) of knee and/or hand OA (P = 8 x 10(-8)) and also with a 30% increased risk of knee OA progression (95% confidence interval 1.03-1.64) (P = 0.03). This SNP is in almost complete linkage disequilibrium with rs3757713 (68 kb upstream of GPR22), which is associated with GPR22 expression levels in lymphoblast cell lines (P = 4 x 10(-12)). Immunohistochemistry experiments revealed that G protein-coupled receptor protein 22 (GPR22) was absent in normal mouse articular cartilage or synovium. However, GPR22-positive chondrocytes were found in the upper layers of the articular cartila...Continue Reading

Citations

Aug 3, 2011·Current Reviews in Musculoskeletal Medicine·R Krishna Chaganti, Nancy E Lane
Feb 19, 2013·Expert Reviews in Molecular Medicine·Louise N Reynard, John Loughlin
May 9, 2012·Proceedings of the National Academy of Sciences of the United States of America·Martha C Castaño BetancourtJoyce B J van Meurs
Jan 6, 2011·Current Opinion in Rheumatology·Tuhina Neogi, Yuqing Zhang
Dec 20, 2012·Current Opinion in Rheumatology·Marc C HochbergBraxton D Mitchell
Nov 12, 2010·Annals of the Rheumatic Diseases·Evangelos EvangelouUNKNOWN Translation Research in Europe Applied Technologies for Osteoarthritis (TreatOA)
Dec 24, 2010·Annals of the Rheumatic Diseases·K PanoutsopoulouJ Loughlin
Jul 23, 2013·Journal of Medical Genetics·Kalliope Panoutsopoulou, Eleftheria Zeggini
Mar 6, 2012·BMC Medical Genetics·Madhushika RatnayakeJohn Loughlin
Mar 19, 2013·BMC Musculoskeletal Disorders·Emma V A RaineJohn Loughlin
Aug 1, 2015·International Journal of Endocrinology·Thomas Mabey, Sittisak Honsawek
Apr 24, 2014·Arthritis & Rheumatology·Cristina Rodriguez-FontenlaAntonio Gonzalez
Sep 18, 2020·Arthritis & Rheumatology·Nikolas H KazmersMichael J Jurynec

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