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To investigate the shared genetic factors and pathways between SS and T1D, we conducted a comprehensive analysis using multiomic approaches. Conditional and conjunctional false discovery rate analyses were performed to identify genetic polygenicity and overlap between the two diseases. Functional annotation and pathway analysis identified SNPs with regulatory potential. Furthermore, Mendelian Randomization (MR) analyses were employed to investigate causal associations between gene expression and disease risk. Single\u2010cell differential gene expression analysis was also employed to validate the associations of risk genes with T1D and SS. Our analysis identified 36 shared loci, revealing common genetic enrichment between SS and T1D. Functional annotation and pathway analysis revealed 52 credible genes involved in cysteine\u2010related processes, apoptotic signalling and immune responses. MR analyses revealed that AC007283.5 was positively linked with both SS and T1D, while PLEKHM1 and CRHR1\u2010T1 were negatively associated. Additionally, CERS2 was positively associated with SS, DEF6 was positively associated with T1D, and KANSL1\u2010AS1 was negatively associated with T1D, indicating the presence of complex regulatory mechanisms. Moreover, Single\u2010cell differential gene expression analysis confirmed the dysregulation of risk genes in SS and T1D. This study identified shared genetic factors and pathways underlying SS and T1D, highlighting cysteine\u2010related processes and apoptotic signalling. The findings underscore the complex interplay of autoimmunity and the need for targeted treatments addressing their common mechanisms.<\/jats:p>","DOI":"10.1111\/jcmm.70930","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T11:48:08Z","timestamp":1764157688000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Crosstalk Between Type 1 Diabetes and Sj\u00f6gren's Syndrome: A Systematic Exploration of Risk Genes and Common Pathways"],"prefix":"10.1111","volume":"29","author":[{"given":"Aamir","family":"Fahira","sequence":"first","affiliation":[{"name":"Dongguan Key Laboratory of Computer\u2010Aided Drug Design, The First Dongguan Affiliated Hospital Guangdong Medical University  Dongguan Guangdong China"},{"name":"Guangdong Medical University Key Laboratory of Big Data Mining and Precision Drug Design, Guangdong Provincial Key Laboratory for Research and Development of 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