Exome analysis of Indian ulcerative colitis reveals novel genes affecting epithelial integrity, DNA repair, trafficking, and immune signalling.
6 affiliations
- 1Department of Biotechnology, School of Engineering and Applied Sciences, Bennett University, Greater Noida, 201310, Uttar Pradesh, India.
- 2Department of Genetics, University of Delhi South Campus, New Delhi, 110021, India.
- 3Dayanand Medical College and Hospital, Ludhiana, 141001, Punjab, India.
- 4Institute of Behavioural Science, Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA.
- 5Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, 11004, USA.
- 6Department of Biotechnology, School of Engineering and Applied Sciences, Bennett University, Greater Noida, 201310, Uttar Pradesh, India. [email protected].
Abstract
Purpose
The genetic component of ulcerative colitis (UC) remains largely unexplained in non-European populations. This study aimed to investigate the polygenic architecture of UC in an Indian population.Methods
Whole-exome sequencing was performed in 160 UC patients and 379 ethnically matched controls. Gene-based rare variant burden tests (SKAT-O, CMC) and exome-wide association testing of coding and noncoding common variants using allelic chi-square testing were performed.Results
Burden analysis identified 85 previously unreported genes significantly enriched for rare variants in UC, of which 22 showed suggestive associations (P ≤ 5 × 10⁻³; odds ratio 2.6-10.9). These genes were primarily involved in epithelial integrity, immune signalling, DNA repair, and vesicle trafficking pathways. Exome-wide association analysis identified 55 common variants surpassing the Bonferroni-corrected significance threshold (P ≤ 5.57 × 10⁻⁷), mapping to 44 unreported and two known susceptibility genes, with most belonging to functional categories similar to those observed in the rare variant analysis. Logistic regression analysis showed that variants significant in the allelic test remained significant after adjustment for covariates. STRING network analysis revealed functional interactions between eight genes identified in this study and known inflammatory bowel disease-related genes. Sub-phenotype analysis further indicated genetic heterogeneity among clinically defined UC subgroups.Conclusion
This first exome-based study of Indian UC patients expands the genetic landscape of the disease and identifies population-specific associations that appear distinct from those reported in Western cohorts, suggesting potential differences in underlying disease mechanisms. Most identified genes map to disease-relevant pathways. However, given the modest sample size and limited statistical power, these findings should be considered exploratory and require further validation to clarify their contribution to UC pathogenesis. The study also underscores the importance of conducting genetic investigations in genetically diverse and understudied populations to improve the broader applicability of genetic findings.
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BibTeX
@article{chauhan2026exome,
title = {{Exome analysis of Indian ulcerative colitis reveals novel genes affecting epithelial integrity, DNA repair, trafficking, and immune signalling.}},
author = {Radhika Chauhan and Bhawna Sharma and Ajit Sood and Vandana Midha and Arshdeep Singh and Jibin John and Garima Juyal},
journal = {Human genomics},
year = {2026},
month = aug,
doi = {10.1186/s40246-026-00994-z},
url = {https://europepmc.org/article/MED/42972604},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Exome analysis of Indian ulcerative colitis reveals novel genes affecting epithelial integrity, DNA repair, trafficking, and immune signalling.
AU - Radhika Chauhan
AU - Bhawna Sharma
AU - Ajit Sood
AU - Vandana Midha
AU - Arshdeep Singh
AU - Jibin John
AU - Garima Juyal
PY - 2026
DA - 2026/08/05
JO - Human genomics
DO - 10.1186/s40246-026-00994-z
UR - https://europepmc.org/article/MED/42972604
AB - Purpose The genetic component of ulcerative colitis (UC) remains largely unexplained in non-European populations. This study aimed to investigate the polygenic architecture of UC in an Indian population.Methods Whole-exome sequencing was performed in 160 UC patients and 379 ethnically matched controls. Gene-based rare variant burden tests (SKAT-O, CMC) and exome-wide association testing of coding and noncoding common variants using allelic chi-square testing were performed.Results Burden analysis identified 85 previously unreported genes significantly enriched for rare variants in UC, of which 22 showed suggestive associations (P ≤ 5 × 10⁻³; odds ratio 2.6-10.9). These genes were primarily involved in epithelial integrity, immune signalling, DNA repair, and vesicle trafficking pathways. Exome-wide association analysis identified 55 common variants surpassing the Bonferroni-corrected significance threshold (P ≤ 5.57 × 10⁻⁷), mapping to 44 unreported and two known susceptibility genes, with most belonging to functional categories similar to those observed in the rare variant analysis. Logistic regression analysis showed that variants significant in the allelic test remained significant after adjustment for covariates. STRING network analysis revealed functional interactions between eight genes identified in this study and known inflammatory bowel disease-related genes. Sub-phenotype analysis further indicated genetic heterogeneity among clinically defined UC subgroups.Conclusion This first exome-based study of Indian UC patients expands the genetic landscape of the disease and identifies population-specific associations that appear distinct from those reported in Western cohorts, suggesting potential differences in underlying disease mechanisms. Most identified genes map to disease-relevant pathways. However, given the modest sample size and limited statistical power, these findings should be considered exploratory and require further validation to clarify their contribution to UC pathogenesis. The study also underscores the importance of conducting genetic investigations in genetically diverse and understudied populations to improve the broader applicability of genetic findings.
SN - 1473-9542
SN - 1479-7364
ER -