Investigation of association between hip osteoarthritis susceptibility loci and radiographic proximal femur shape.
Investigation of association between hip osteoarthritis susceptibility loci and radiographic proximal femur shape.
复制标题
DOI：
10.1002/art.39186
复制
发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Wallis GA
中科院分区：
文献类型：
--
作者：
Lindner C;Thiagarajah S;Wilkinson JM;Panoutsopoulou K;Day-Williams AG;arcOGEN Consortium;Cootes TF;Wallis GA
检验先前报告的髋关节形态或骨关节炎（OA）易感位点是否与股骨近端形状相关，如统计形状模型（SSM）模式所示，并作为单变量或多变量定量性状。我们使用了来自929名单侧髋关节OA受试者的骨盆X线片和基因型数据，这些受试者之前曾被招募参加英国关节炎研究骨关节炎遗传学联盟的全基因组关联研究。我们构建了3个SSM，用于捕获整个混合性别队列和男性/女性分层队列中OA未受影响的股骨近端的形状变化。我们选择了41个候选单核苷酸多态性（SNP），这些SNP先前被报道为与髋关节形态（用于复制分析）或OA（用于发现分析）相关，并且基因型数据可用。我们对这些SNP和SSM模式之间的基因型-表型关联进行了2种类型的分析：1）使用单个SSM模式的单变量分析和2）使用SSM模式组合的多变量分析。单变量分析确定了rs 4836732（ASTN 2基因内）与女性SSM模式5之间的关联（P = 0.0016）以及rs6976（GLT 8D 1基因内）与混合性别SSM模式7之间的关联（P = 0.0003）。多变量分析确定了rs 5009270（靠近IFRD 1基因）与混合性别SSM模式3、4和9的组合之间的关联（P = 0.0004）。相关性的证据仍然显着调整后的多重测试。所有3个SNP先前都与髋关节OA相关。这些新发结果表明，rs 4836732、rs6976和rs 5009270可能通过改变股骨近端形状而导致髋关节OA易感性。
To test whether previously reported hip morphology or osteoarthritis (OA) susceptibility loci are associated with proximal femur shape as represented by statistical shape model (SSM) modes and as univariate or multivariate quantitative traits. We used pelvic radiographs and genotype data from 929 subjects with unilateral hip OA who had been recruited previously for the Arthritis Research UK Osteoarthritis Genetics Consortium genome‐wide association study. We built 3 SSMs capturing the shape variation of the OA‐unaffected proximal femur in the entire mixed‐sex cohort and for male/female‐stratified cohorts. We selected 41 candidate single‐nucleotide polymorphisms (SNPs) previously reported as being associated with hip morphology (for replication analysis) or OA (for discovery analysis) and for which genotype data were available. We performed 2 types of analysis for genotype–phenotype associations between these SNPs and the modes of the SSMs: 1) a univariate analysis using individual SSM modes and 2) a multivariate analysis using combinations of SSM modes. The univariate analysis identified association between rs4836732 (within the ASTN2 gene) and mode 5 of the female SSM (P = 0.0016) and between rs6976 (within the GLT8D1 gene) and mode 7 of the mixed‐sex SSM (P = 0.0003). The multivariate analysis identified association between rs5009270 (near the IFRD1 gene) and a combination of modes 3, 4, and 9 of the mixed‐sex SSM (P = 0.0004). Evidence of associations remained significant following adjustment for multiple testing. All 3 SNPs had previously been associated with hip OA. These de novo findings suggest that rs4836732, rs6976, and rs5009270 may contribute to hip OA susceptibility by altering proximal femur shape.