Assessing the genetic relationships between osteoarthritis and human plasma proteins: a large scale genetic correlation scan
Assessing the genetic relationships between osteoarthritis and human plasma proteins: a large scale genetic correlation scan
复制标题
评估骨关节炎和人类血浆蛋白之间的遗传关系：大规模遗传相关扫描
DOI：
10.21037/atm-19-4643
复制
发表时间：
2020-06-01
影响因子：
--
通讯作者：
Zhang, Feng
中科院分区：
文献类型：
--
作者：
Liu, Li;Wang, Sen;Zhang, Feng
背景：骨关节炎（OA）是一种多因素的复杂疾病。血浆蛋白对OA的影响目前尚不清楚。方法：采用英国生物银行OA全基因组关联研究数据。使用Affymetrix UK BiLEVE Axiom或UK Biobank Axiom阵列进行全基因组SNP基因分型。同样，3622个血浆蛋白的GWAS汇总数据来自最近发表的一项研究。因此，我们采用连锁不平衡评分回归（LD评分回归）分析来评估每种血浆蛋白与OA不同位点之间的遗传相关性。结果：鉴定出几种提示OA的血浆蛋白。对于手部OA， α -胰蛋白酶抑制剂重链H1（系数= -0.3854，P值= 0.0198）和多重肌醇多磷酸磷酸酶1（系数= -1.1721，P值= 0.0303）存在遗传相关性。髋部OA有7个提示基因相关信号，如跨膜糖蛋白NMB（系数= 0.6944，P值= 0.0098）、内皮细胞特异性分子1（系数= 0.6337，P值= 0.03）。对于膝关节OA，鉴定出12个提示性遗传相关信号，包括Elafin（系数= -0.5562，P值= 0.0092）、Interleukin-16（系数= 0.3949，P值= 0.0435）。结论：我们系统地研究了血浆蛋白与OA不同部位的遗传相关性。我们的结果提供了新的证据，OA是一种异质性疾病。
Background: Osteoarthritis (OA) is a multifactorial complex disease. The impact of plasma proteins on OA remains elusive now.Methods: The UK Biobank genome-wide association study data of OA was used here. Genome-wide SNP genotyping was performed using the Affymetrix UK BiLEVE Axiom or UK Biobank Axiom array. Equally, the GWAS summary data of 3,622 plasma proteins was derived from a recently published study. Consequently, linkage disequilibrium score regression (LD score regression) analysis was performed to evaluate the genetic correlation between each plasma protein and different sites of OA.Results: Several suggestive plasma proteins were identified for OA. For hand OA, evidence of genetic correlation was observed for inter-alpha- trypsin inhibitor heavy chain H1 (coefficient = -0.3854, P value = 0.0198), multiple inositol polyphosphate phosphatase 1 (coefficient = -1.1721, P value = 0.0303). For hip OA, 7 suggestive genetic correlation signals were observed, such as Transmembrane glycoprotein NMB (coefficient = 0.6944, P value = 0.0098), Endothelial cell-specific molecule 1 (coefficient = 0.6337, P value = 0.03). For Knee OA, 12 suggestive genetic correlation signals were identified, including Elafin (coefficient = -0.5562, P value = 0.0092), Interleukin-16 (coefficient = 0.3949, P value = 0.0435).Conclusions: We investigated the genetic correlations between plasma proteins and different sites of OA in a systematic way. Our results provide novel evidence that OA is a heterogeneous disease.