Evidence map›Paper›PMID 41664201›Full record

ArticleJournal of ovarian research2026

Unraveling the role of lipid metabolism in polycystic ovary syndrome through multi-omics Mendelian randomization.

Ronghuan He, Xiaoyu Tu, Bei Liu, Zeyi Jiang, Jin Chen, Jingyi Li

Abstract read
In one paragraph

Article in Journal of ovarian research, 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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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Ronghuan He *Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Zhejiang, 310006, China.
Xiaoyu Tu *Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Zhejiang, 310006, China.
Bei LiuDepartment of Reproductive Genetics, Women's Hospital, Zhejiang University School of Medicine, Zhejiang, 310006, China.
Zeyi JiangSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Jin ChenSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Jingyi LiDepartment of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Zhejiang, 310006, China. 06yxsyljy@zju.edu.cn.

Funding

Natural Science Foundation of Zhejiang Province LMS25H040002
6 · The paper itself

Abstract

backgroundPolycystic ovary syndrome (PCOS) is increasingly recognized as a metabolic disorder, with dysregulated lipid metabolism emerging as a key factor in its pathogenesis. However, the precise mechanisms underlying this relationship remain unclear. We employed a summary data-based Mendelian randomization (SMR) approach to investigate the potential causal relationships between lipid metabolism-related genes and PCOS. First, we integrated PCOS genome-wide association study (GWAS) data from the Finngen_R11_E4_PCOS cohort with three layers of blood-based molecular quantitative trait loci (QTLs): methylation QTLs (mQTLs), expression QTLs (eQTLs), and protein QTLs (pQTLs). To ensure the robustness of the SMR signals, we performed the heterogeneity in dependent instruments (HEIDI) test to detect potential horizontal pleiotropy and conducted colocalization analysis to identify shared potential causal genetic variants. Findings were validated in two independent cohorts: Phenocode_265.4 and Felix. We then integrated mQTL and eQTL data to further dissect methylation-mediated gene expression regulation. Finally, we examined the expression profiles of key candidate genes using publicly available transcriptomic datasets from the Gene Expression Omnibus (GEO) database.

resultsSMR analysis in the discovery cohort identified 132 mQTLs (corresponding to 70 genes), 16 eQTLs, and 7 pQTLs associated with PCOS. Among these, 71 mQTLs (corresponding to 39 genes), 11 eQTLs, and 4 pQTLs were supported by strong colocalization evidence. Further validation in the Phenocode_265.4 and Felix cohorts confirmed the association of 13 mQTLs (corresponding to 7 genes) and 2 eQTLs with PCOS. Specifically, the associations of ACOX2 (cg22012981), GLIPR1 (cg01554451), and PIK3R3 (cg27584146) with PCOS were further supported by subsequent analyses. mQTL‑eQTL SMR analysis confirmed the negative regulatory effects of these methylation sites on the expression of their corresponding genes. Finally, transcriptomic data revealed upregulation of GLIPR1 and PIK3R3 in tissues from patients with PCOS.

conclusionThis study shows the association of lipid metabolism-related genes, particularly ACOX2, PIK3R3, and GLIPR1, with PCOS pathogenesis. These findings highlight them as candidates for further functional studies and potential future therapeutic development.

Indexed as

Lipid MetabolismMendelian Randomization AnalysisPolycystic Ovary SyndromeDNA MethylationFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMultiomicsPolymorphism, Single NucleotideQuantitative Trait LociColocalizationLipid metabolismMendelian randomizationMulti-OmicsPolycystic ovary syndrome

Identifiers

PMID41664201
PMCPMC12983665

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.