No evidence of an association between mitochondrial DNA variants and osteoarthritis in 7393 cases and 5122 controls

Abstract

Objectives: Osteoarthritis (OA) has a complex aetiology with a strong genetic component. Genome-wide association studies implicate several nuclear genes in the aetiology, but a major component of the heritability has yet to be defined at the molecular level. Initial studies implicate maternally inherited variants of mitochondrial DNA (mtDNA) in subgroups of patients with OA based on gender and specific joint involvement, but these findings have not been replicated.

Methods: The authors studied 138 maternally inherited mtDNA variants genotyped in a two cohort genetic association study across a total of 7393 OA cases from the arcOGEN consortium and 5122 controls genotyped in the Wellcome Trust Case Control consortium 2 study.

Results: Following data quality control we examined 48 mtDNA variants that were common in cohort 1 and cohort 2, and found no association with OA. None of the phenotypic subgroups previously associated with mtDNA haplogroups were associated in this study.

Conclusions: We were not able to replicate previously published findings in the largest mtDNA association study to date. The evidence linking OA to mtDNA is not compelling at present.

Figure 1

Principal components analysis (PCA) performed on raw fluorescent intensities in the pooled data set of 7393 osteoarthritis (OA) cases and 5122 controls. The PCA provided independent confirmation of the European haplogroup structure. There was no significant difference in the cluster distribution between OA cases and controls (online supplementary table S4). 58C, WTCCC MRC 1958 birth cohort control genotypes; ARC1, arcOGEN cohort 1; ARC2, arcOGEN cohort 2; NBS, WTCCC national blood transfusion service control genotypes; WTCCC, Wellcome Trust Case Control Consortium. This figure is only reproduced in colour in the online version.