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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1417899

A genome-wide cross-trait analysis identifying shared genetic basis and causal relationships between Hunner-type interstitial cystitis and autoimmune diseases in East Asian populations

Provisionally accepted
Xinyi Lyu Xinyi Lyu 1Liao Peng Liao Peng 1Xueyuan Xu Xueyuan Xu 1Yang Fan Yang Fan 1Yong Yang Yong Yang 1Jiawei Chen Jiawei Chen 1Mengzhu Liu Mengzhu Liu 1Yuanzhuo Chen Yuanzhuo Chen 1Chi Zhang Chi Zhang 1Shiqin Yang Shiqin Yang 1Sihong Shen Sihong Shen 1Jie Zhang Jie Zhang 1Xiao Zeng Xiao Zeng 1Hong Shen Hong Shen 1Deyi Luo Deyi Luo 1Yifei Lin Yifei Lin 1,2*
  • 1 West China Hospital, Sichuan University, Chengdu, China
  • 2 Harvard Chan School Center for Work, Health, and Well-being, School of Public Health, Harvard University, Boston, Massachusetts, United States

The final, formatted version of the article will be published soon.

    Purpose: Epidemiological studies have demonstrated the clinical link between Hunner interstitial cystitis (HIC) and autoimmune diseases (ADs), suggesting potential shared genetic bases for their comorbidity. We aimed to investigate the shared genetic architecture and causal relationships between HIC and ADs.We conducted a genome-wide cross-trait study with ~170000 individuals of East Asian ancestry to investigate the shared architecture between HIC and ADs. Bidirectional Mendelian randomization (MR) was used to assess potential causal relationships and a multi-trait analysis of GWAS (MTAG) was conducted to identify their associated pleiotropic loci. Fine-mapping analysis narrowed candidate gene susceptibility loci and colocalization analysis was performed to identify shared variants at specific locus. Lastly, transcriptome-wide association (TWAS) and functional analysis were utilized to explore potential shared gene-tissue associations.Results: Through bidirectional MR analysis, we observed a positive causal effect of AIH(ORIVW=1.09, PIVW=1.00×10 -3 ) and RA (ORIVW=1.47, PIVW<1.00×10 -4 ) on HIC and a negative causal effect of UC on HIC (ORIVW=0.89, PIVW< 1.00×10 -4 ).Furthermore, we unveiled a robust positive causal effect of HIC on T1D(ORConMix=1.05, PConMix=1.77×10 -3 ). Cross-trait meta-analysis identified a total of 64 independent SNPs associated with HIC and ADs. Functional analysis revealed that the identified variants regulated gene expression in major tissues belonging to the autoimmune system. Conclusions: Our findings might offer insights into the shared underlying etiology of HIC and ADs.

    Keywords: Cross-trait analysis, genetic epidemiology, Mendelian randomization, Hunner-type interstitial cystitis, Autoimmune disorder SS: Sjögren's syndrome T1D: Type 1 diabetes mellitus TWAS: Transcriptome-wide association studies UC: Ulcerative colitis UV: Uveitis WM: Weighted-medium

    Received: 15 Apr 2024; Accepted: 28 Oct 2024.

    Copyright: © 2024 Lyu, Peng, Xu, Fan, Yang, Chen, Liu, Chen, Zhang, Yang, Shen, Zhang, Zeng, Shen, Luo and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yifei Lin, West China Hospital, Sichuan University, Chengdu, China

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