Integrating Genetics With Epidemiological Measurements Identifies Burden QTLs of Inflammatory Bowel Disease across 20 Countries.

Authors

Chen Sun, Siyu Wei, Junxian Tao, Haiyan Chen, Chi Yan, Jiacheng Wang, Jing Xu, Lian Duan, Yuanbo Zhan, Yuping Zou, Ruilin Li, Linna Yuan, Wei She, Songlin Lu, Ning Wang, Qinduo Ren, Yan Guo, Yuan Xu, Chang Wang, Hongsheng Tian, Chen Zhang, Yu Dong, Guoping Tang, Zhenwei Shang, Yongshuai Jiang, Wenhua Lv, Mingming Zhang, Hongchao Lyu

Published in

Advanced science (Weinheim, Baden-Wurttemberg, Germany). Pages e19007. Sep 27, 2026. Epub Sep 27, 2026.

Abstract

It remains unclear whether the observed heterogeneity in the burden of inflammatory bowel disease (IBD) across countries is associated with differences in population genetic structure. To address this problem, we performed a burden quantitative trait locus (bQTL) analysis, integrating epidemiological data (1990-2021) from the Global Burden of Disease (GBD) study with genotypes of 2 621 978 SNPs from 2414 unrelated individuals in the 1000 Genomes Project across 20 matched countries. We identified 1074 bQTLs of IBD, of which 384 were significantly associated with both the age-standardized prevalence rate and age-standardized incidence rate. rs7633471 (chr3:30698616:C>A) showed the strongest effect: each increase in centi-allele frequency (CAF) of the allele C was associated with a 10.00 decrease in age-standardized prevalence rate and a 1.02 decrease in age-standardized incidence rate. Pathway analysis revealed that bQTLs were primarily enriched in synaptic membrane, voltage-gated potassium channel complex, and potassium channel complex. Through fine-mapping, we further identified 800 putative causal variants for IBD, with significant findings located within genes related to the immune system (IGSF21 and CSMD2), inflammatory response (SMPDL3B and AOAH), and intestinal cancers (FHIT and CSMD2). Our study provides the first comprehensive characterization of the genetic architecture underlying the global burden of IBD.

PMID:
42801564
Bibliographic data and abstract were imported from PubMed on 28 Sep 2026.

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