Frontiers in Immunology (Nov 2024)
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
- Xinyi Lyu,
- Xinyi Lyu,
- Liao Peng,
- Liao Peng,
- Xueyuan Xu,
- Xueyuan Xu,
- Yang Fan,
- Yang Fan,
- Yong Yang,
- Yong Yang,
- Yong Yang,
- Jiawei Chen,
- Jiawei Chen,
- Mengzhu Liu,
- Mengzhu Liu,
- Yuanzhuo Chen,
- Yuanzhuo Chen,
- Chi Zhang,
- Chi Zhang,
- Shiqin Yang,
- Shiqin Yang,
- Sihong Shen,
- Sihong Shen,
- Jie Zhang,
- Jie Zhang,
- Xiao Zeng,
- Xiao Zeng,
- Hong Shen,
- Hong Shen,
- Deyi Luo,
- Deyi Luo,
- Yifei Lin,
- Yifei Lin
Affiliations
- Xinyi Lyu
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Xinyi Lyu
- Pelvic Floor Diseases Center, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
- Liao Peng
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Liao Peng
- Pelvic Floor Diseases Center, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
- Xueyuan Xu
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Xueyuan Xu
- Pelvic Floor Diseases Center, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
- Yang Fan
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Yang Fan
- Pelvic Floor Diseases Center, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
- Yong Yang
- Health Management Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Yong Yang
- General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Yong Yang
- Medical Device Regulatory Research and Evaluation Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Jiawei Chen
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Jiawei Chen
- Pelvic Floor Diseases Center, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
- Mengzhu Liu
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Mengzhu Liu
- Institute of Urology, Beijing Municipal Health Commission, Beijing, China
- Yuanzhuo Chen
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Yuanzhuo Chen
- Pelvic Floor Diseases Center, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
- Chi Zhang
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Chi Zhang
- Pelvic Floor Diseases Center, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
- Shiqin Yang
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Shiqin Yang
- Pelvic Floor Diseases Center, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
- Sihong Shen
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Sihong Shen
- Pelvic Floor Diseases Center, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
- Jie Zhang
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Jie Zhang
- Pelvic Floor Diseases Center, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
- Xiao Zeng
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Xiao Zeng
- Pelvic Floor Diseases Center, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
- Hong Shen
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Hong Shen
- Pelvic Floor Diseases Center, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
- Deyi Luo
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Deyi Luo
- Pelvic Floor Diseases Center, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, China
- Yifei Lin
- Department of Urology, Lab of Health Data Science, Innovation Institute for Integration of Medicine and Engineering, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Yifei Lin
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- DOI
- https://doi.org/10.3389/fimmu.2024.1417899
- Journal volume & issue
-
Vol. 15
Abstract
PurposeEpidemiological 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.MethodsWe 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.ResultsThrough 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.ConclusionsOur 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
