IBMS BoneKEy | BoneKEy Watch
GWAS suggest small number of new candidate genes for osteoarthritis
DOI:10.1038/bonekey.2014.99
Osteoarthritis is a common illness with a complex genetic background. Genome wide association studies (GWAS) have been used to identify new candidate genes in two different populations; one in Iceland and the other in northern Europe (UK and The Netherlands).
The GWAS performed by Styrkarsdottir et al. looked for genes associated with severe hand osteoarthritis. Starting with 623 people with this condition, they then used 69 153 people as population controls, testing for associations between over 34 million sequence variants, identified by whole genome sequencing of 2230 Icelanders.
Two significantly associated loci were pinpointed, one at 15q22, from common sequence variants in the ALDH1A2 gene (aldehyde dehydrogenase 1 family, member A2) and one from much rarer sequence variants on chromosome 1 at 1p31. Mutations at this second locus were detected in a single Icelandic family in which there were a large number of cases of severe hand arthritis and generalized osteoarthritis.
Rodriguez-Fontenla et al. used the Human Genome Epidemiology Navigator to identify 199 potential gene candidates. They focused on single-nucleotide polymorphisms (SNPs) with an allele frequency lower than 5% and then compared them with the meta-analysis results of nine GWAS.
These were generated from 5636 patients with osteoarthritis of the knee, with 16 972 population controls and from 4349 patients with osteoarthritis of the hip, with 17 836 population controls. The controls were derived from individuals with European ancestry. A further 5921 people were then assessed for the SNPs that were found to be significantly associated with osteoarthritis.
Only two SNPs, one in the COL11A1 gene (collagen, type XI, alpha 1) and the other in the gene that encodes vascular endothelial growth factor, were found to be significantly associated with osteoarthritis of the hip.
Editor’s comment: The results of the latter study are reminiscent of the similar exercise by Richards et al. in which 150 candidate genes were tested for association with osteoporosis, and only nine were found to correlate with reduced bone mineral density.
This work is licensed under a
Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.