Lazanas Panagiotis, Antonatos Charalabos, Tsoumani Konstantina T, Sgourou Argyro, Vasilopoulos Yiannis
Laboratory of Genetics, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece.
Biology Laboratory, School of Science and Technology, Hellenic Open University, 26504 Patras, Greece.
Int J Mol Sci. 2025 Sep 18;26(18):9124. doi: 10.3390/ijms26189124.
Atopic dermatitis (AD) and autoimmune diseases exhibit epidemiological comorbidity, yet the shared genetic architecture remains incompletely understood. We investigated the genetic overlap between AD and three autoimmune disorders including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and vitiligo, leveraging genome-wide association data. Despite modest evidence for global genetic correlations, we found 113 independent pleiotropic loci shared among AD and autoimmune diseases, with 11 displaying a concordant effect across all 3 pairwise comparisons. Gene-set and tissue enrichment analyses evidenced the inflammatory background of pleiotropic associations. Multi-trait colocalization analysis prioritized 22 loci, linking the tissue-specific expression of , , , , , , and pleiotropic genes with AD risk. Mendelian randomization revealed no causal effect of genetic liability to AD on autoimmune diseases. Nevertheless, genetic liability to IBD increased AD risk, while vitiligo exhibited a protective effect post outlier correction. Our findings provide mechanistic insights into the multimorbidity of atopic dermatitis (AD) and autoimmune diseases, offering additional evidence for the pleiotropic genetic architecture of AD that contributes to systemic immune dysregulation across multiple organ systems.
特应性皮炎（AD）与自身免疫性疾病存在流行病学共病现象，但其共享的遗传结构仍未完全明确。我们利用全基因组关联数据，研究了AD与三种自身免疫性疾病（包括炎症性肠病（IBD）、类风湿性关节炎（RA）和白癜风）之间的遗传重叠情况。尽管全球遗传相关性证据有限，但我们发现AD与自身免疫性疾病之间共有113个独立的多效性位点，其中11个在所有3对比较中均显示出一致的效应。基因集和组织富集分析证明了多效性关联的炎症背景。多性状共定位分析确定了22个位点，将多效性基因、、、、、和的组织特异性表达与AD风险联系起来。孟德尔随机化分析表明，AD的遗传易感性对自身免疫性疾病无因果效应。然而，IBD的遗传易感性增加了AD风险，而白癜风在异常值校正后表现出保护作用。我们的研究结果为特应性皮炎（AD）和自身免疫性疾病的共病机制提供了见解，为AD的多效性遗传结构提供了额外证据，该结构导致多个器官系统的全身免疫失调。
