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Published on: May 2, 2022
Shared Genetic Basis Between Systemic Lupus Erythematosus and Inflammatory Bowel Disease in East Asian Ancestry: A
Xiaoxiao Mo1,2, Hui Mo3, Chao Wang1,2
1Department of Environmental Genomics and Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Abstract:
Systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD) are both categorized as autoimmune disorders and have similar non-specific gastrointestinal symptoms. SLE and IBD have shown shared genetic architecture in European ancestry; however, given the ancestry-specificity of genetic architecture, the shared genetic structure in East Asian ancestry remains unclear. This study reveals significant global and local genetic overlap between SLE and IBD subtypes in East Asian ancestry by using genetic correlation analyses. Cross-trait and colocalization analyses identify 64 shared loci and 19 causal variant credible sets between SLE and IBD subtypes. Notably, pleiotropic genes (HIC2, UBE2L3, ARAP1, ATG16L2, ANKS1A, and TULP1) were validated through Gene Expression Omnibus databases and previous studies. The major histocompatibility complex region emerges as a critical hub for shared genetic correlations and pleiotropic effects in SLE-IBD pathogenesis. Gene-level enrichment analyses implicate chemokine and lipid binding as underlying shared biological mechanisms.
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