全基因组关联研究鉴定出与免疫和腺体细胞功能相关的干燥综合征风险基因座。
Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells.
机构信息
Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
出版信息
Nat Commun. 2022 Jul 27;13(1):4287. doi: 10.1038/s41467-022-30773-y.
Sjögren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.
干燥综合征是一种复杂的自身免疫性疾病，有十二个已确定的易感基因位点。这项全基因组关联研究（GWAS）确定了欧洲血统干燥综合征患者的十个新的全基因组显著（GWS）区域：CD247、NAB1、PTTG1-MIR146A、PRDM1-ATG5、TNFAIP3、XKR6、MAPT-CRHR1、RPTOR-CHMP6-BAIAP6、TYK2、SYNGR1。多基因风险评分具有可预测性（AUROC=0.71）和 12.08 的相对风险。对生物信息学数据库的查询细化了关联，定义了 95%置信区间内 GWS SNP 的局部调控网络，并将涉及的基因列表扩展到>40 个。许多 GWS SNP 是免疫细胞中拓扑相关结构域内基因的 eQTL 和/或主要靶组织唾液腺中的 eQTL。
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