International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.
International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.
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DOI：
10.1038/ncomms9019
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发表时间：
2015-09-22
影响因子：
16.6
通讯作者：
Siminovitch KA
中科院分区：
文献类型：
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作者：
Cordell HJ;Han Y;Mells GF;Li Y;Hirschfield GM;Greene CS;Xie G;Juran BD;Zhu D;Qian DC;Floyd JA;Morley KI;Prati D;Lleo A;Cusi D;Canadian-US PBC Consortium;Italian PBC Genetics Study Group;UK-PBC Consortium;Gershwin ME;Anderson CA;Lazaridis KN;Invernizzi P;Seldin MF;Sandford RN;Amos CI;Siminovitch KA
原发性胆汁性肝硬化（PBC）是一种经典的自身免疫性肝病，目前缺乏有效的免疫调节治疗。在这里，我们对来自欧洲受试者（n= 2，764例病例和10，475例对照）的全基因组关联研究的发现数据集进行荟萃分析，然后在一个独立队列（n= 3，716例病例和4，261例对照）中进行验证基因分型。我们发现并验证了6个先前未知的PBC风险位点（P结合<5 × 10−8），并使用通路分析来识别JAK-STAT/IL 12/IL 27信号通路和丝氨酸-细胞因子通路，并对其进行了相关治疗。 原发性胆汁性肝硬化是一种自身免疫性肝病，治疗选择很少。Cordell等人对欧洲全基因组关联研究进行了荟萃分析，确定了六个新的风险位点和一些潜在的治疗途径。
Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist. Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.