Candidate Loci are Revealed by an Initial Genome-wide Association Study of Juvenile Osteochondritis Dissecans.

Background: Osteochondritis dissecans (OCD) is a condition that oftentimes causes significant knee pain in pediatric patient populations. If left untreated, OCD significantly increases the risk of developing degenerative osteoarthritis along with its associated consequences and costs. Although a genetic component has been suggested to play a role in this disorder, few studies have been carried out in order to determine the underlying genetic etiology of this relatively common complex trait. The goal of our study was to perform an initial genome-wide association study (GWAS) to uncover candidate loci associated with the pathogenesis of OCD.

Methods: Blood samples were acquired from 2 cohorts, aged 0 to 18 years old, consisting of 209 OCD cases and 1855 population-matched controls. Agencourt Genfind DNA isolation technology was used to isolate high-quality DNA from each sample. Genotype data was then generated utilizing the Illumina Infinium BeadChip array to examine single-nucleotide polymorphisms (SNPs).

Results: In an initial GWAS analysis of our cohort, where a SNP was excluded if the Hardy-Weinberg Equilibrium test P<0.0001, the minor allele frequency<5%, and the genotyping call rate<90%, we obtained our first results for OCD. Although there was no SNP strictly reaching the threshold for genome-wide significance at this early stage, multiple SNPs (35) at several loci revealed evidence of suggestive association with OCD (P<5.0×10).

Conclusions: The results from our preliminary study are encouraging. Herein we not only discuss the relevance and applicability of GWAS in studying a genetic basis for OCD, but have also identified top signals that may suggest loci involved in coordinated expression as well as a transcription factor involved in development that may be highly relevant to this trait.

Clinical Relevance: If genetic predispositions for OCD are detected early enough in life, attempts at activity modification, counseling, and orthopaedic monitoring may successfully reduce progression of this condition, which may lead to progressive osteoarthritis in the third to fourth decade in at-risk patients.