Single-Cell Immune Cis-eQTL Mendelian Randomization Prioritizes Cell-Type-Resolved Candidate Causal Genes for Endometriosis
- 1Department of Urology, The Second People’s Hospital of Wuhu, Wuhu, Anhui, People’s Republic of China
Abstract
Background: Endometriosis has a substantial immune component, but the cellular contexts of genetically regulated disease susceptibility remain incompletely resolved.
Methods: We tested single-cell cis-eQTL instruments from 20 OneK1K peripheral-blood cell types against FinnGen R12 endometriosis (20,190 cases; 130,160 controls) using single-variant Mendelian randomization (MR), colocalization and sensitivity analyses. Benjamini–Yekutieli (BY) correction distinguished conservative findings from an exploratory Benjamini–Hochberg (BH) screen. Directional consistency, bulk-blood MR and lesion expression provided contextual comparisons.
Results: Across 9157 unique gene–cell-type tests, 135 associations in 61 genes reached BH-FDR < 0.05. Colocalization at the default prior prioritized 10 genes (6 protein-coding) across 28 pairs. LOC102723878 and RUVBL1 were also BY-robust; IGF1R in natural killer (NK) cells was BH-supported but not BY-robust (PP4 = 0.89; OR 1.11 per SD higher expression). Its NK attribution reflects instrument availability and does not establish exclusivity. Colocalization was prior-sensitive. Directional concordance in a partly overlapping sample (8/8) was descriptive. Bulk-blood MR nominated 3/6 testable protein-coding genes. IGF1R lesion expression showed a nonsignificant upward trend (P = 0.101).
Conclusion: The analysis prioritizes immune-context candidate genes for functional study. IGF1R remains an exploratory, mechanistically unresolved nomination. Genetic support and protein tractability do not establish therapeutic benefit or reproductive safety; experimental validation is required.
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BibTeX
@article{wang2026singlecell,
title = {{Single-Cell Immune Cis-eQTL Mendelian Randomization Prioritizes Cell-Type-Resolved Candidate Causal Genes for Endometriosis}},
author = {Xin Wang and Guanglei Yao and Wei Ding},
journal = {International Journal of Women's Health},
year = {2026},
month = oct,
doi = {10.2147/ijwh.s643362},
url = {https://doi.org/10.2147/ijwh.s643362},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Single-Cell Immune Cis-eQTL Mendelian Randomization Prioritizes Cell-Type-Resolved Candidate Causal Genes for Endometriosis
AU - Xin Wang
AU - Guanglei Yao
AU - Wei Ding
PY - 2026
DA - 2026/10/30
JO - International Journal of Women's Health
DO - 10.2147/ijwh.s643362
UR - https://doi.org/10.2147/ijwh.s643362
AB - Background: Endometriosis has a substantial immune component, but the cellular contexts of genetically regulated disease susceptibility remain incompletely resolved. Methods: We tested single-cell cis-eQTL instruments from 20 OneK1K peripheral-blood cell types against FinnGen R12 endometriosis (20,190 cases; 130,160 controls) using single-variant Mendelian randomization (MR), colocalization and sensitivity analyses. Benjamini–Yekutieli (BY) correction distinguished conservative findings from an exploratory Benjamini–Hochberg (BH) screen. Directional consistency, bulk-blood MR and lesion expression provided contextual comparisons. Results: Across 9157 unique gene–cell-type tests, 135 associations in 61 genes reached BH-FDR < 0.05. Colocalization at the default prior prioritized 10 genes (6 protein-coding) across 28 pairs. LOC102723878 and RUVBL1 were also BY-robust; IGF1R in natural killer (NK) cells was BH-supported but not BY-robust (PP4 = 0.89; OR 1.11 per SD higher expression). Its NK attribution reflects instrument availability and does not establish exclusivity. Colocalization was prior-sensitive. Directional concordance in a partly overlapping sample (8/8) was descriptive. Bulk-blood MR nominated 3/6 testable protein-coding genes. IGF1R lesion expression showed a nonsignificant upward trend (P = 0.101). Conclusion: The analysis prioritizes immune-context candidate genes for functional study. IGF1R remains an exploratory, mechanistically unresolved nomination. Genetic support and protein tractability do not establish therapeutic benefit or reproductive safety; experimental validation is required.
SN - 1179-1411
ER -