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PreprintCited by 15Ovarian function and disordersGenetic Associations and EpidemiologyGenetic and Kidney Cyst Diseases

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Mendelian randomization analysis identified potential genes pleiotropically associated with polycystic ovary syndrome

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Sun, Qian, Yuan, Gao, Yang, Jingyun, Lu, Jiayi, Feng, Wen, Yang, Wen·2021·Reproductive Sciences
DOI 10.1101/2021.06.29.21259512PMC PMC8547723

Preprint — published as 10.1007/s43032-021-00776-z

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Abstract

Research question: Polycystic ovary syndrome (PCOS) is a common endocrine disorder with unclear etiology. Are there any genes that are pleiotropically or potentially causally associated with PCOS? Design: We applied the summary data-based Mendelian randomization (SMR) method integrating genome-wide association study (GWAS) for PCOS and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with PCOS. We performed separate SMR analysis using eQTL data in the ovary and whole blood. Results: Although no genes showed significant pleiotropic association with PCOS after correction for multiple testing, some of the genes exhibited suggestive significance. RPS26 showed the strongest suggestive pleiotropic association with PCOS in both SMR analyses (β[SE]=0.10[0.03], P SMR =1.72×10 −4 for ovary; β[SE]=0.11[0.03], P SMR =1.40×10 −4 for whole blood). PM20D1 showed the second strongest suggestive pleiotropic association with PCOS in the SMR analysis using eQTL data for the whole blood, and was also among the top ten hit genes in the SMR analysis using eQTL data for the ovary. Two other genes, including CTC-457L16 . 2 and NEIL2 , were among the top ten hit genes in both SMR analyses. Conclusion: We identified multiple genes that were potentially involved in the pathogenesis of PCOS. Our findings provided helpful leads to a better understanding of the mechanisms underlying PCOS, and revealed potential therapeutic targets for the effective treatment of PCOS. KEY MESSAGE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and its etiology can be multifaceted. We found that multiple genes were potentially involved in the pathogenesis of PCOS. The findings revealed the genetic mechanisms underlying PCOS and potential therapeutic targets for the effective treatment of PCOS.

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  • Preliminary evidence suggests that several genes related to obesity, metabolic and reproductive function may play a causal role in the pathogenesis of PCOS.

    “Nevertheless, preliminary evidence suggests that several genes related to obesity, metabolic and reproductive function, may play a causal role in the pathogenesis of PCOS [90,91].”

    From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [91]

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References 56 · Cited by 15

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Metadata

Authors
Sun, Q., Yuan, G., Yang, J., Lu, J., Feng, W., & Yang, W.
Affiliations
  • The First People’s Hospital of Lianyungang (CN)
  • Rush University Medical Center (US)
  • Shanghai University (CN)
  • Kangda College of Nanjing Medical University (CN)
ORCID
Venue
Reproductive Sciences
Publisher
openRxiv
Published
2021-07-03
Volume
29
Issue
3
Pages
1028-1037
ISSN
1933-7191 (ISSN-L)
DOI
10.1101/2021.06.29.21259512
PMC
PMC8547723
OpenAlex
W3209849700
Cited by
15
References
56
Citations by year
2026: 5 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 4
FWCI
1.94
Type
journal article
Language
en
Open access
Locations
  • Reproductive Sciences (publishedVersion)
  • medRxiv (acceptedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (R01AG36042)
  • National Institute on Aging (R01AG017917, R01AG36042, P30-AG 10161, R01‐AG17917, R01 AG15819, U01‐AG61356, R01AG015819, P30AG010161, U01AG061356, RF1AG064312)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
Keywords
polycystic ovary syndrome, pleiotropy, RPS26, PM20D1, NEIL2, expression quantitative trait loci, ovarian gene expression, whole blood gene expression, causal genes, PCOS pathogenesis
MeSH terms
Female, Humans, Polycystic Ovary Syndrome, Ribosomal Proteins, Genetic Predisposition to Disease, Quantitative Trait Loci, DNA-(Apurinic or Apyrimidinic Site) Lyase, DNA Glycosylases, Genome-Wide Association Study, Mendelian Randomization Analysis

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