Open Access Open Badges Research article

Allelic expression analysis of the osteoarthritis susceptibility locus that maps to chromosome 3p21 reveals cis-acting eQTLs at GNL3 and SPCS1

Fiona Gee*, Clare F Clubbs, Emma VA Raine, Louise N Reynard and John Loughlin

Author Affiliations

Institute of Cellular Medicine, Musculoskeletal Research Group, Newcastle University, Newcastle-upon-Tyne, UK

For all author emails, please log on.

BMC Medical Genetics 2014, 15:53  doi:10.1186/1471-2350-15-53

Published: 4 May 2014



An osteoarthritis (OA) susceptibility locus has been mapped to chromosome 3p21, to a region of high linkage disequilibrium encompassing twelve genes. Six of these genes are expressed in joint tissues and we therefore assessed whether any of the six were subject to cis-acting regulatory polymorphisms active in these tissues and which could therefore account for the association signal.


We measured allelic expression using pyrosequencing assays that can distinguish mRNA output from each allele of a transcript single nucleotide polymorphism. We assessed RNA extracted from the cartilage and other joint tissues of OA patients who had undergone elective joint replacement surgery. A two-tailed Mann–Whitney exact test was used to test the significance of any allelic differences.


GNL3 and SPCS1 demonstrated significant allelic expression imbalance (AEI) in OA cartilage (GNL3, mean AEI = 1.04, p = 0.0002; SPCS1, mean AEI = 1.07, p < 0.0001). Similar results were observed in other tissues. Expression of the OA-associated allele was lower than that of the non-associated allele for both genes.


cis-acting regulatory polymorphisms acting on GNL3 and SPCS1 contribute to the OA association signal at chromosome 3p21, and these genes therefore merit further investigation.

Osteoarthritis; Genetic risk; Single nucleotide polymorphism; Allelic imbalance; Linkage disequilibrium