Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study

Abstract

ObjectivesThe genetic aetiology of osteoarthritis has not yet been elucidated. To enable a well-powered genome-wide association study (GWAS) for osteoarthritis, the authors have formed the arcOGEN Consortium, a UK-wide collaborative effort aiming to scan genome-wide over 7500 osteoarthritis cases in a two-stage genome-wide association scan. Here the authors report the findings of the stage 1 interim analysis.MethodsThe authors have performed a genome-wide association scan for knee and hip osteoarthritis in 3177 cases and 4894 population-based controls from the UK. Replication of promising signals was carried out in silico in five further scans (44 449 individuals), and de novo in 14 534 independent samples, all of European descent.ResultsNone of the association signals the authors identified reach genome-wide levels of statistical significance, therefore stressing the need for corroboration in sample sets of a larger size. Application of analytical approaches to examine the allelic architecture of disease to the stage 1 genome-wide association scan data suggests that osteoarthritis is a highly polygenic disease with multiple risk variants conferring small effects.ConclusionsIdentifying loci conferring susceptibility to osteoarthritis will require large-scale sample sizes and well-defined phenotypes to minimise heterogeneity.

Contribution of genetic and epigenetic mechanisms to Wnt pathway activity in prevalent skeletal disorders

“…However, this has not been replicated in other reports, including some 406 recent genome-wide studies (Panoutsopoulou et al, 2011).…”

“…(Arcogen Consortium, 2012;Panoutsopoulou et al, 2011 been related to osteoporosis in genetic association studies (Ralston,90 2010; Riancho et al, 2011;Richards et al, 2009;Styrkarsdottir et al, 91 2009; Valero et al, 2011 …”

Renal Kallikrein Excretion and Epigenetics in Human Acute Kidney Injury: Expression, Mechanisms and Consequences

“…This has given support to the hypothesis of a developmental origin of osteoarthritis [102 104]. The importance of developmental factors is also emphasized by recent results from genome-wide association studies [105,106]. Somewhat unexpectedly, these studies have not revealed significant associations between osteoarthritis and genes typically involved in cartilage homeostasis, such as those encoding proteases.…”

The Impact of Large-Scale Genomic Methods in Orthopaedic Disorders: Insights from Genome-Wide Association Studies

“…Another orthopaedic condition, osteoarthritis, has also been intensively investigated by GWASs. Identifying clearly replicated signals has proven challenging, but potential candidate genes that are worthy of further investigation have been identified [45][46][47][48][49][50][51][52][53] . Although we expect that larger ongoing GWASs will replicate the known associations, we expect that such investigations will also identify new genes that yield novel insights into osteoporosis and osteoarthritis.…”