Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
Ann Rheum Dis. 2011 May;70(5):864-7. doi: 10.1136/ard.2010.141473. Epub 2010 Dec 21.
The 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.
The 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.
None 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.
Identifying loci conferring susceptibility to osteoarthritis will require large-scale sample sizes and well-defined phenotypes to minimise heterogeneity.
骨关节炎的遗传病因尚未阐明。为了能够对骨关节炎进行强大的全基因组关联研究（GWAS），作者成立了 arcOGEN 联盟，这是一个英国范围内的合作努力，旨在对 7500 多例骨关节炎病例进行两阶段全基因组关联扫描。在此，作者报告了第一阶段中期分析的结果。
作者对来自英国的 3177 例膝关节和髋关节骨关节炎病例和 4894 名基于人群的对照进行了全基因组关联扫描。在另外五次扫描（44449 人）中进行了有希望信号的虚拟复制，并在 14534 个独立样本中进行了从头复制，所有样本均为欧洲血统。
作者确定的关联信号均未达到全基因组统计学意义水平，因此强调需要在更大样本量的样本集中进行证实。将分析方法应用于研究疾病等位基因结构的全基因组关联扫描数据表明，骨关节炎是一种高度多基因疾病，多种风险变异赋予了较小的影响。
确定易患骨关节炎的基因座需要大规模的样本量和明确的表型，以最小化异质性。
