Wiley Mandi M, Khatri Bhuwan, Joachims Michelle L, Tessneer Kandice L, Stolarczyk Anna M, Rasmussen Astrid, Anaya Juan-Manuel, Aqrawi Lara A, Bae Sang-Cheol, Baecklund Eva, Björk Albin, Brun Johan G, Bucher Sara Magnusson, Dand Nick, Eloranta Maija-Leena, Engelke Fiona, Forsblad-d'Elia Helena, Fugmann Cecilia, Glenn Stuart B, Gong Chen, Gottenberg Jacques-Eric, Hammenfors Daniel, Imgenberg-Kreuz Juliana, Jensen Janicke Liaaen, Johnsen Svein Joar Auglænd, Jonsson Malin V, Kelly Jennifer A, Khanam Sharmily, Kim Kwangwoo, Kvarnström Marika, Mandl Thomas, Martín Javier, Morris David L, Nocturne Gaetane, Norheim Katrine Brække, Olsson Peter, Palm Øyvind, Pers Jacques-Olivier, Rhodus Nelson L, Sjöwall Christopher, Skarstein Kathrine, Taylor Kimberly E, Tombleson Phil, Thorlacius Gudny Ella, Venuturupalli Swamy, Vital Edward M, Wallace Daniel J, Grundahl Kiely M, Radfar Lida, Brennan Michael T, James Judith A, Scofield R Hal, Gaffney Patrick M, Criswell Lindsey A, Jonsson Roland, Appel Silke, Eriksson Per, Bowman Simon J, Omdal Roald, Rönnblom Lars, Warner Blake M, Rischmueller Maureen, Witte Torsten, Farris A Darise, Mariette Xavier, Shiboski Caroline H, Wahren-Herlenius Marie, Alarcón-Riquelme Marta E, Ng Wan-Fai, Sivils Kathy L, Guthridge Joel M, Adrianto Indra, Vyse Timothy J, Tsao Betty P, Nordmark Gunnel, Lessard Christopher J
Genes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
Arthritis and Clinical Immunology Research Program, OMRF, Oklahoma City, Oklahoma, USA.
bioRxiv. 2023 Oct 6:2023.10.05.561076. doi: 10.1101/2023.10.05.561076.
Fine mapping and bioinformatic analysis of the genetic risk association in Sjögren's Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on and expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including . Collectively, functional characterization implicated the risk alleles of these SNPs as modulators of promoter and/or enhancer activities that regulate cell type-specific expression of , , and , among others. Further, these findings emphasize the importance of exploring the functional significance of SNPs in the context of complex chromatin architecture in disease-relevant cell types and tissues.
对干燥综合征（SjD）和系统性红斑狼疮（SLE）中遗传风险关联进行精细定位和生物信息学分析，确定了五个在免疫细胞类型中有功能证据的常见单核苷酸多态性（SNP）：rs4938573、rs57494551、rs4938572、rs4936443、rs7117261。对免疫细胞、唾液腺上皮细胞和肾上皮细胞中核蛋白结合亲和力、增强子/启动子调控活性以及染色质-染色质相互作用进行功能研究，发现所有这五个SNP都具有细胞类型特异性等位基因效应，其调控作用超出了对[具体基因]表达的影响。绘制局部染色质调控网络揭示了几个其他感兴趣的基因，包括[具体基因]。总体而言，功能特征表明这些SNP的风险等位基因是启动子和/或增强子活性的调节因子，可调节[多个基因]等的细胞类型特异性表达。此外，这些发现强调了在疾病相关细胞类型和组织的复杂染色质结构背景下探索SNP功能意义的重要性。
