Using genetics to identify cell types and mechanisms underlying susceptibility to primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a T-cell mediated, chronic inflammatory condition of the biliary tree that is strongly associated with inflammatory bowel disease. Genome-wide association studies have identified 22 non-HLA genetic risk variants associated PSC. Identifying the genes impacted by these variants has proven difficult as the majority lie in non-coding regions of the genome. Knowledge of the genes and biological pathways these non-coding variants are perturbing is vital to understanding the disease biology. One means of assessing the impact of non-coding variants within disease associated loci upon genes is via colocalisation with eQTL. Many eQTL are cell-type specific, requiring the analysis of disease relevant cell types to detect colocalisation. We have collected PSC-relevant T-cell-subtypes from the peripheral blood of PSC patients via fluorescence activated cell sorting in preparation for RNA sequencing and mapping of eQTL. Samples were collected at the Norfolk and Norwich University Hopital, for which local ethical approval has been granted. Lysed cell samples will be transferred to WTSI and DNA/RNA will be extracted from lysed cell samples by T143 before genotyping (DNA) and custom library preparation and sequencing (RNA).
This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/EGA study EGAS00001002642

原发性硬化性胆管炎（Primary sclerosing cholangitis, PSC）是一种由T细胞介导的胆道慢性炎症性疾病，与炎症性肠病存在显著相关性。全基因组关联研究已鉴定出22个与PSC相关的非HLA遗传风险变异。由于绝大多数变异位于基因组非编码区域，鉴定这些变异所调控的基因一直颇具挑战。明确这些非编码变异所扰动的基因及生物学通路，对于解析该疾病的发病机制至关重要。评估疾病关联位点内非编码变异对基因的影响，可通过与表达数量性状位点（expression quantitative trait locus, eQTL）共定位的方式实现。多数eQTL具有细胞类型特异性，因此需针对疾病相关细胞类型开展分析以检测共定位事件。本研究通过荧光激活细胞分选术，从PSC患者外周血中分离得到PSC相关T细胞亚型，用于后续RNA测序及eQTL定位分析。样本采集于诺福克与诺里奇大学医院，已获得当地伦理委员会批准。裂解后的细胞样本将被移送至WTSI，由T143团队完成DNA与RNA提取，随后分别开展DNA基因分型及RNA定制化文库制备与测序。
本数据集属于预发布数据。若需了解惠康桑格研究所（Wellcome Trust Sanger Institute）共享的预发布数据的规范使用方式（含出版禁运相关细则），请访问http://www.sanger.ac.uk/datasharing/，对应EGA研究编号为EGAS00001002642。