Evidence map›Paper›PMID 42701819›Full record

ArticleInternational journal of women's health2026

Genetically Predicted Gene Expression and Circulating Metabolites Associated with Cervical High-Grade Squamous Intraepithelial Lesion: A Mendelian Randomization Study.

Bozhou Cui, Yan Ding, Feixia Li, Tuoyang Hu, Jiaojiao Zhu, Xiaoying Chang, Yucun Wang, Jie Yang, Jing Cui

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Article in International journal of women's health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

9 authors.

Bozhou Cui *Department of Experimental Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710038, People's Republic of China.
Yan DingDepartment of Gynecological Oncology, Cancer Hospital of Gansu Province, Lanzhou, Gansu, 730000, People's Republic of China.
Feixia LiDepartment of Gynecological Oncology, Cancer Hospital of Gansu Province, Lanzhou, Gansu, 730000, People's Republic of China.
Tuoyang HuDepartment of Gynecological Oncology, Cancer Hospital of Gansu Province, Lanzhou, Gansu, 730000, People's Republic of China.
Jiaojiao ZhuDepartment of Gynecological Oncology, Cancer Hospital of Gansu Province, Lanzhou, Gansu, 730000, People's Republic of China.
Xiaoying ChangDepartment of Gynecological Oncology, Cancer Hospital of Gansu Province, Lanzhou, Gansu, 730000, People's Republic of China.
Yucun WangDepartment of Gynecological Oncology, Cancer Hospital of Gansu Province, Lanzhou, Gansu, 730000, People's Republic of China.
Jie YangEndoscopic Diagnosis and Treatment Center, Gansu Provincial hospital, Lanzhou, Gansu, 730000, People's Republic of China.
Jing Cui *Department of Gynecological Oncology, Cancer Hospital of Gansu Province, Lanzhou, Gansu, 730000, People's Republic of China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: High-grade squamous intraepithelial lesion (HSIL) is a precancerous condition of the cervix. Identifying risk factors associated with HSIL and understanding their potential mechanisms may inform prevention strategies. This study aimed to investigate the associations of genetically predicted gene expression and circulating metabolites with HSIL risk using Mendelian randomization (MR). Methods: We performed two-sample MR analysis to evaluate the associations of genetically predicted gene expression (eQTLGen consortium, N=31,684) and circulating metabolites (genome-wide association study [GWAS], N=8,299) with HSIL risk (FinnGen R12, N=293,218; 8,291 cases). Mediation analysis was conducted to explore whether metabolites might mediate the associations between genes and HSIL. Sensitivity analyses, including Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), leave-one-out, and colocalization, were performed to assess the robustness of the findings. All GWAS data used in this study were derived from European-ancestry populations. Results: Eleven genes showed significant associations with HSIL after false discovery rate (FDR) correction (q<0.05), including VWA7, PAX8, GUSBP1, IKZF3, PAX8-AS1, NFKBIL1 (interpret with caution due to an influential single nucleotide polymorphism [SNP]), ERBB2, COL11A2, SKIV2L, TCF19, and PGAP3. Eleven circulating metabolites were also significantly associated with HSIL. Mediation analysis suggested that two phospholipid metabolites (GCST90200685 and GCST90200692) might mediate a small proportion of the total protective association of COL11A2 with HSIL (1.46% and 1.45%, respectively), indicating that the protective association of COL11A2 is largely independent of these circulating metabolites. Colocalization analysis showed strong evidence of shared causal variants for eight genes (PP.H4>0.98), while COL11A2 showed weak evidence of colocalization (PP.H4=1.58×10 Conclusion: This MR study identified 11 genes and 11 circulating metabolites associated with HSIL risk. Among these, COL11A2 showed a protective association that appeared to be largely independent of circulating phospholipid metabolites, suggesting potential local mechanisms. These findings provide genetic and metabolic clues for future studies on HSIL etiology.

Indexed as

cervical HSILcirculating metabolitesCOL11A2mediation analysisMendelian randomization

Identifiers

PMID42701819
PMCPMC13546070

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