Gut Microbiota, Inflammatory Bowel Disease and the Prioritization of Host Effector Genes: A Two-Sample Mendelian Randomization Study with Independent Replication, cis-eQTL Colocalization and Single-Cell Localization.
- 1School of Medicine, Guangxi University, No. 100 Daxue East Road, Nanning 530004, China.
Abstract
Gut microbial dysbiosis is common in inflammatory bowel disease (IBD), but whether specific taxa are causal, and through which host genes, remains unclear. We integrated two-sample Mendelian randomization (MR), replication, cis-eQTL colocalization, and single-cell mapping to identify microbial taxa with genetically predicted associations and candidate host mediators. Instruments for 211 taxa from MiBioGen (p < 1×10⁻⁵, r² < 0.001) were used in two-sample MR (inverse-variance weighted IVW primary; sensitivity: Egger, weighted median, MR-PRESSO) against IBD, Crohn's disease (CD), and ulcerative colitis (UC) in the International IBD Genetics Consortium (IIBDGC), with false discovery rate (FDR) correction. Replication was conducted in FinnGen R12; gene prioritization was performed via cis-SMR/coloc.abf using GTEx v8/CAGE eQTLs, and localization in 11,175 colonic cells. MR identified 15 significant associations (FDR < 0.05) across eight features; applying a pre-specified heterogeneity-based rule, 13 across seven independent features were retained as primary associations (strongest NB1n → CD, OR 1.32) and two were downgraded to suggestive; at the independent-signal level, three of 11 associations were replicated and seven were direction-concordant in FinnGen. Colocalization supported shared variants at SENP7 (blood, CD PP.H4 = 0.86, IBD = 0.70) and ZBTB11-AS1 (colon, IBD = 0.76, CD = 0.74); single-cell analysis mapped SENP7 to T/NK, and ZBTB11-AS1/VIPR1 to epithelial/goblet. Replicated MR and colocalization prioritized SENP7 (whole-blood eQTL; minor T/NK-cell detection) and ZBTB11-AS1 (colon epithelium) as candidate effectors, though the latter lacks functional characterization.
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BibTeX
@article{zou2026microbiota,
title = {{Gut Microbiota, Inflammatory Bowel Disease and the Prioritization of Host Effector Genes: A Two-Sample Mendelian Randomization Study with Independent Replication, cis-eQTL Colocalization and Single-Cell Localization.}},
author = {Qiyuan Zou and Jianyi Wang},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198718},
url = {https://europepmc.org/article/MED/42883969},
note = {CC BY},
}
RIS
TY - JOUR
TI - Gut Microbiota, Inflammatory Bowel Disease and the Prioritization of Host Effector Genes: A Two-Sample Mendelian Randomization Study with Independent Replication, cis-eQTL Colocalization and Single-Cell Localization.
AU - Qiyuan Zou
AU - Jianyi Wang
PY - 2026
DA - 2026/09/29
JO - International journal of molecular sciences
DO - 10.3390/ijms27198718
UR - https://europepmc.org/article/MED/42883969
AB - Gut microbial dysbiosis is common in inflammatory bowel disease (IBD), but whether specific taxa are causal, and through which host genes, remains unclear. We integrated two-sample Mendelian randomization (MR), replication, cis-eQTL colocalization, and single-cell mapping to identify microbial taxa with genetically predicted associations and candidate host mediators. Instruments for 211 taxa from MiBioGen (p < 1×10⁻⁵, r² < 0.001) were used in two-sample MR (inverse-variance weighted IVW primary; sensitivity: Egger, weighted median, MR-PRESSO) against IBD, Crohn's disease (CD), and ulcerative colitis (UC) in the International IBD Genetics Consortium (IIBDGC), with false discovery rate (FDR) correction. Replication was conducted in FinnGen R12; gene prioritization was performed via cis-SMR/coloc.abf using GTEx v8/CAGE eQTLs, and localization in 11,175 colonic cells. MR identified 15 significant associations (FDR < 0.05) across eight features; applying a pre-specified heterogeneity-based rule, 13 across seven independent features were retained as primary associations (strongest NB1n → CD, OR 1.32) and two were downgraded to suggestive; at the independent-signal level, three of 11 associations were replicated and seven were direction-concordant in FinnGen. Colocalization supported shared variants at SENP7 (blood, CD PP.H4 = 0.86, IBD = 0.70) and ZBTB11-AS1 (colon, IBD = 0.76, CD = 0.74); single-cell analysis mapped SENP7 to T/NK, and ZBTB11-AS1/VIPR1 to epithelial/goblet. Replicated MR and colocalization prioritized SENP7 (whole-blood eQTL; minor T/NK-cell detection) and ZBTB11-AS1 (colon epithelium) as candidate effectors, though the latter lacks functional characterization.
SN - 1422-0067
ER -