Jordana Jampel

DocwireNews

A research group aimed to investigate the shared genetic architecture and causal relationships between Hunner interstitial cystitis (HIC) and autoimmune diseases (ADs) in terms of genetic bases for their comorbidity.
The study, <a href="https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1417899/full">published</a> in Frontiers in Immunology, comprised a genome-wide cross-trait study (GWAS) with approximately 170,000 individuals of east Asian ancestry to investigate the shared architecture between HIC and ADs. The ADs included were atopic dermatitis, autoimmune hepatitis, allergic rhinitis, asthma, contact dermatitis, Graves’ disease, Hashimoto’s thyroiditis, hypothyroidism, hyperthyroidism, myasthenia gravis, pollinosis, psoriasis vulgaris, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, Sjögren’s syndrome, type 1 diabetes, ulcerative colitis, and uveitis.
Bidirectional Mendelian randomization was used to assess potential causal relationships, and a multi-trait analysis of GWAS was conducted to identify their associated pleiotropic loci. Fine-mapping analysis narrowed candidate gene susceptibility loci, and colocalization analysis was performed to identify their associated pleiotropic loci. Fine-mapping analysis was performed to identify shared variants at specific locus. Lastly, transcriptome-wide association and functional analysis were utilized to explore potential shared gene-tissue associations.
Through bidirectional Mendelian randomization analysis, the researchers observed a positive causal effect of autoimmune hepatitis (overall response [OR]IVW, 1.09; PIVW=1.00×10-3) and rheumatoid arthritis (ORIVW, 1.47; PIVW&lt;1.00×10-4) on HIC and a negative causal effect of ulcerative colitis on HIC (ORIVW, 0.89; PIVW&lt; 1.00×10-4). A robust positive causal effect of HIC on type 1 diabetes (ORConMix, 1.05; PConMix=1.77×10-3) was revealed.
Cross-trait meta-analysis identified a total of 64 independent single nucleotide polymorphism associated with HIC and ADs, specifically autoimmune hepatitis, rheumatoid arthritis, and type 1 diabetes, at genome-wide significant levels. The researchers also discovered that the HLA region plays a significant role in linking HIC and ADs. This suggests that associated risk SNPs may contribute to disease by affecting protein function rather than regulating transcription levels.
“In addition, we discovered multiple potential common biological mechanisms that can enhance our knowledge of the link between HIC and ADs. These discoveries open up new avenues for future research on functional validation, disease prevention, and clinical treatment strategies,” the researchers concluded.

A research group aimed to investigate the shared genetic architecture and causal relationships between Hunner interstitial cystitis (HIC) and autoimmune diseases (ADs) in terms of genetic bases for their comorbidity.The study, <a href="https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1417899/full">published</a> in Frontiers in Immunology, comprised a genome-wide cross-trait study (GWAS) with approximately 170,000 individuals of east Asian ancestry to investigate the shared architecture between HIC and ADs. The ADs included were atopic dermatitis, autoimmune hepatitis, allergic rhinitis, asthma, contact dermatitis, Graves’ disease, Hashimoto’s thyroiditis, hypothyroidism, hyperthyroidism, myasthenia gravis, pollinosis, psoriasis vulgaris, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, Sjögren’s syndrome, type 1 diabetes, ulcerative colitis, and uveitis.Bidirectional Mendelian randomization was used to assess potential causal relationships, and a multi-trait analysis of GWAS was conducted to identify their associated pleiotropic loci. Fine-mapping analysis narrowed candidate gene susceptibility loci, and colocalization analysis was performed to identify their associated pleiotropic loci. Fine-mapping analysis was performed to identify shared variants at specific locus. Lastly, transcriptome-wide association and functional analysis were utilized to explore potential shared gene-tissue associations.Through bidirectional Mendelian randomization analysis, the researchers observed a positive causal effect of autoimmune hepatitis (overall response [OR]IVW, 1.09; PIVW=1.00×10-3) and rheumatoid arthritis (ORIVW, 1.47; PIVW&lt;1.00×10-4) on HIC and a negative causal effect of ulcerative colitis on HIC (ORIVW, 0.89; PIVW&lt; 1.00×10-4). A robust positive causal effect of HIC on type 1 diabetes (ORConMix, 1.05; PConMix=1.77×10-3) was revealed.Cross-trait meta-analysis identified a total of 64 independent single nucleotide polymorphism associated with HIC and ADs, specifically autoimmune hepatitis, rheumatoid arthritis, and type 1 diabetes, at genome-wide significant levels. The researchers also discovered that the HLA region plays a significant role in linking HIC and ADs. This suggests that associated risk SNPs may contribute to disease by affecting protein function rather than regulating transcription levels.“In addition, we discovered multiple potential common biological mechanisms that can enhance our knowledge of the link between HIC and ADs. These discoveries open up new avenues for future research on functional validation, disease prevention, and clinical treatment strategies,” the researchers concluded.

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Bidirectional Mendelian randomization was used and a multi-trait analysis of GWAS was conducted. 

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