Skip to main content Accessibility help
×
Hostname: page-component-77c78cf97d-9dm9z Total loading time: 0 Render date: 2026-04-25T23:25:52.959Z Has data issue: false hasContentIssue false

Chapter 2 - Polycystic Ovary Syndrome: From Phenotype to Genotype

Published online by Cambridge University Press:  13 May 2022

By
Joop S. E. Laven  and
Yvonne V. Louwers
Edited by
Gabor T. Kovacs ,
Bart Fauser  and
Richard S. Legro
Gabor T. Kovacs
Affiliation:
Monash University, Melbourne, Australia
Bart Fauser
Affiliation:
University Medical Center, Utrecht, Netherlands
Richard S. Legro
Affiliation:
Penn State Medical Center, Hershey, PA, USA
Get access

Summary

The genetic underpinnings of polycystic ovary syndrome (PCOS) implicate neuroendocrine, metabolic and reproductive pathways in the pathogenesis of disease. Although specific phenotype stratified analyses are needed, genetic findings were surprisingly consistent across the diagnostic classifications using former National Institute of Health (NIH) , Rotterdam or AE-PCOS criteria suggesting a common genetic architecture underlying the different phenotypes. Genes identified until now all in some ways involved ovarian function and folliculogenesis. Indeed most of the identified single nucleotide polymorphisms (SNPs) were significantly associated with ovulatory dysfunction, hyperandrogenism and polycystic ovarian morphology (PCOM). Furthermore, there was also genetic evidence for shared biologic pathways between PCOS and a number of metabolic disorders, menopause, depression and male-pattern balding, a putative male phenotype.

Keywords

polycystic ovary syndrome (PCOS)polycystic ovarian morphology (PCOM)ovulatory dysfunctionhyperandrogenismsingle nucleotide polymorphism (SNP)candidate genesgenome-wide association studies (GWAS)phenome-wide association studies (PheWAS)

Information

Type
Chapter
Information
Polycystic Ovary Syndrome , pp. 8 - 20
Publisher: Cambridge University Press
Print publication year: 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19(1): 41–47.CrossRefGoogle Scholar
Fauser, B. C., Tarlatzis, B. C., Rebar, R. W. et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): The Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril 2012; 97(1): 28–38 e25.CrossRefGoogle ScholarPubMed
Teede, H. J., Misso, M. L., Costello, M. F. et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Clin Endocrinol (Oxf) 2018; 89(3): 251–268.Google Scholar
Vink, J. M., Sadrzadeh, S., Lambalk, C. B. and Boomsma, D. I. Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab 2006; 91(6): 2100–2104.Google Scholar
Yilmaz, B., Vellanki, P., Ata, B. and Yildiz, B. O. Metabolic syndrome, hypertension, and hyperlipidemia in mothers, fathers, sisters, and brothers of women with polycystic ovary syndrome: A systematic review and meta-analysis. Fertil Steril 2018; 109(2): 356–364 e332.CrossRefGoogle ScholarPubMed
Joo, Y. Y., Actkins, K., Pacheco, J. A. et al. A polygenic and phenotypic risk prediction for polycystic ovary syndrome evaluated by phenome-wide association studies. J Clin Endocrinol Metab 2020; 105(6): 1918–1936. https://doi.org/10.1210/clinem/dgz326CrossRefGoogle ScholarPubMed
Hiam, D., Moreno-Asso, A., Teede, H. J. et al. The genetics of polycystic ovary syndrome: An overview of candidate gene systematic reviews and genome-wide association studies. J Clin Med 2019; 8(10): 1606.Google Scholar
Laven, J. S. E. Follicle stimulating hormone receptor (FSHR) polymorphisms and polycystic ovary syndrome (PCOS). Front Endocrinol (Lausanne) 2019; 10: 23.CrossRefGoogle ScholarPubMed
Kevenaar, M. E., Laven, J. S., Fong, S. L. et al. A functional anti-Müllerian hormone gene polymorphism is associated with follicle number and androgen levels in polycystic ovary syndrome patients. J Clin Endocrinol Metab 2008; 93(4): 1310–1316.Google Scholar
Gorsic, L. K., Kosova, G., Werstein, B. et al. Pathogenic anti-Müllerian hormone variants in polycystic ovary syndrome. J Clin Endocrinol Metab 2017; 102(8): 2862–2872.CrossRefGoogle ScholarPubMed
Gorsic, L. K., Dapas, M., Legro, R. S., Hayes, M. G. and Urbanek, M. Functional genetic variation in the anti-Müllerian hormone pathway in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2019; 104(7): 2855–2874.CrossRefGoogle ScholarPubMed
Zhao, H., Lv, Y., Li, L. and Chen, Z. J. Genetic studies on polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 2016; 37: 56–65.CrossRefGoogle ScholarPubMed
Zhang, T., Liang, W., Fang, M., Yu, J., Ni, Y. and Li, Z. Association of the CAG repeat polymorphisms in androgen receptor gene with polycystic ovary syndrome: A systemic review and meta-analysis. Gene 2013; 524(2): 161–167.CrossRefGoogle ScholarPubMed
Zhu, J. L., Chen, Z., Feng, W. J., Long, S. L. and Mo, Z. C. Sex hormone-binding globulin and polycystic ovary syndrome. Clin Chim Acta 2019; 499: 142–148.CrossRefGoogle ScholarPubMed
Ruan, Y., Ma, J. and Xie, X. Association of IRS-1 and IRS-2 genes polymorphisms with polycystic ovary syndrome: A meta-analysis. Endocr J 2012; 59(7): 601–609.Google Scholar
Shen, W., Li, T., Hu, Y., Liu, H. and Song, M. Common polymorphisms in the CYP1A1 and CYP11A1 genes and polycystic ovary syndrome risk: A meta-analysis and meta-regression. Arch Gynecol Obstet 2014; 289(1): 107–118.CrossRefGoogle Scholar
Shen, W., Li, T., Hu, Y., Liu, H. and Song, M. Calpain-10 genetic polymorphisms and polycystic ovary syndrome risk: A meta-analysis and meta-regression. Gene 2013; 531(2): 426–434.CrossRefGoogle Scholar
Gao, J., Xue, J. D., Li, Z. C., Zhou, L. and Chen, C. The association of DENND1A gene polymorphisms and polycystic ovary syndrome risk: A systematic review and meta-analysis. Arch Gynecol Obstet 2016; 294(5): 1073–1080.CrossRefGoogle Scholar
Chen, Z. J., Zhao, H., He, L. et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Genet 2011; 43(1): 55–59.CrossRefGoogle ScholarPubMed
Shi, Y., Zhao, H., Shi, Y. et al. Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. Nat Genet 2012; 44(9): 1020–1025.CrossRefGoogle ScholarPubMed
Hwang, J. Y., Lee, E. J., Jin, G. M. et al. Genome-wide association study identifies GYS2 as a novel genetic factor for polycystic ovary syndrome through obesity-related condition. J Hum Genet 2012; 57(10): 660–664.CrossRefGoogle ScholarPubMed
Lee, H., Oh, J. Y., Sung, Y. A. et al. Genome-wide association study identified new susceptibility loci for polycystic ovary syndrome. Hum Reprod 2015; 30(3): 723–731.CrossRefGoogle ScholarPubMed
Hayes, M. G., Urbanek, M., Ehrmann, D. A. et al. Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Nat Commun 2015; 6: 7502.CrossRefGoogle ScholarPubMed
Day, F. R., Hinds, D. A., Tung, J. Y. et al. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nat Commun 2015; 6: 8464.CrossRefGoogle ScholarPubMed
Guo, R., Zheng, Y., Yang, J. and Zheng, N. Association of TNF-alpha, IL-6 and IL-1beta gene polymorphisms with polycystic ovary syndrome: a meta-analysis. BMC Genet 2015; 16(1): 5.CrossRefGoogle ScholarPubMed
Jia, H., Yu, L., Guo, X., Gao, W. and Jiang, Z. Associations of adiponectin gene polymorphisms with polycystic ovary syndrome: A meta-analysis. Endocrine 2012; 42(2): 299–306.Google Scholar
Wu, H., Yu, K. and Yang, Z. Associations between TNF-alpha and interleukin gene polymorphisms with polycystic ovary syndrome risk: A systematic review and meta-analysis. J Assist Reprod Genet 2015; 32(4): 625–634.Google Scholar
Chen, L., Zhang, Z., Huang, J. and Jin, M. Association between rs1800795 polymorphism in the interleukin-6 gene and the risk of polycystic ovary syndrome: A meta-analysis. Medicine (Baltimore) 2018; 97(29): e11558.CrossRefGoogle ScholarPubMed
Yan, J., Tian, Y., Gao, X. et al. A genome-wide association study identifies FSHR rs2300441 associated with follicle-stimulating hormone levels. Clin Genet 2020; 97(6): 869–877.Google Scholar
Day, F., Karaderi, T., Jones, M. R. et al. Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. PLoS Genet 2018; 14(12): e1007813.Google Scholar
Qiu, L., Liu, J. and Hei, Q. M. Association between two polymorphisms of follicle stimulating hormone receptor gene and susceptibility to polycystic ovary syndrome: a meta-analysis. Chin Med Sci J 2015; 30(1): 44–50.Google Scholar
Hong, S. H., Hong, Y. S., Jeong, K., Chung, H., Lee, H. and Sung, Y. A. Relationship between the characteristic traits of polycystic ovary syndrome and susceptibility genes. Sci Rep 2020; 10(1): 10479.CrossRefGoogle ScholarPubMed
Cui, L., Li, G., Zhong, W. et al. Polycystic ovary syndrome susceptibility single nucleotide polymorphisms in women with a single PCOS clinical feature. Hum Reprod 2015; 30(3): 732–736.CrossRefGoogle ScholarPubMed
Carey, A. H., Chan, K. L., Short, F., White, D., Williamson, R. and Franks, S. Evidence for a single gene effect causing polycystic ovaries and male pattern baldness. Clin Endocrinol (Oxf) 1993; 38(6): 653–658.CrossRefGoogle ScholarPubMed
McAllister, J. M., Legro, R. S., Modi, B. P. and Strauss, J. F., 3rd. Functional genomics of PCOS: From GWAS to molecular mechanisms. Trends Endocrinol Metab 2015; 26(3): 118–124.Google Scholar
McAllister, J. M., Modi, B., Miller, et al. Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype. Proc Natl Acad Sci U S A 2014; 111(15): E1519–1527.CrossRefGoogle ScholarPubMed
Dapas, M., Lin, F. T. J., Nadkarni, G. N. et al. Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis. PLoS Med 2020; 17(6): e1003132.CrossRefGoogle ScholarPubMed
Deshmukh, H., Papageorgiou, M., Kilpatrick, E. S., Atkin, S. L. and Sathyapalan, T. Development of a novel risk prediction and risk stratification score for polycystic ovary syndrome. Clin Endocrinol (Oxf) 2019; 90(1): 162–169.Google Scholar
Jiang, X., Li, J., Zhang, B. et al. Differential expression profile of plasma exosomal microRNAs in women with polycystic ovary syndrome. Fertil Steril 2021; 115(3): 782–792.CrossRefGoogle ScholarPubMed
Kamalidehghan, B., Habibi, M., Afjeh, S. S. et al. The importance of small non-coding RNAs in human reproduction: A review article. Appl Clin Genet 2020; 13: 1–11.Google Scholar

Accessibility standard: Unknown

Why this information is here

This section outlines the accessibility features of this content - including support for screen readers, full keyboard navigation and high-contrast display options. This may not be relevant for you.

Accessibility Information

Accessibility compliance for the HTML of this chapter is currently unknown and may be updated in the future.

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×