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Causes and Consequences of Polycystic Ovary Syndrome: Insights From Mendelian Randomization
Open accessAbstract
Context: Although polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age, risk factors that may cause the syndrome are poorly understood. Based on epidemiologic studies, PCOS is thought to cause several adverse outcomes such as cardiovascular disease; however, the common presence of comorbidities such as obesity may be responsible for such associations, rather than PCOS in and of itself. To overcome the limitations of observational studies, investigators have employed Mendelian randomization (MR), which uses genetic variants to interrogate causality between exposures and outcomes. Evidence Acquisition: To clarify causes and consequences of PCOS, this review will describe MR studies involving PCOS, both as an exposure and as an outcome. The literature was searched using the terms “Mendelian randomization,” “polycystic ovary syndrome,” “polycystic ovarian syndrome,” and “PCOS” (to May 2021). Evidence Synthesis: MR studies have suggested that obesity, testosterone levels, fasting insulin, serum sex hormone-binding globulin concentrations, menopause timing, male-pattern balding, and depression may play a causal role in PCOS. In turn, PCOS may increase the risk of estrogen receptor–positive breast cancer, decrease the risk of endometrioid ovarian cancer, and have no direct causal effect on type 2 diabetes, coronary heart disease, or stroke. Conclusions: The accumulation of genome-wide association studies in PCOS has enabled multiple MR analyses identifying factors that may cause PCOS or be caused by PCOS. This knowledge will be critical to future development of measures to prevent PCOS in girls at risk as well as prevent complications in those who have PCOS.
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“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 [90]
Citations
Cites
Bowden, J., Davey Smith, G., & Burgess, S. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv080 · Cited by 9,816
Verbanck, M., Chen, C.-Y., Neale, B., & Do, R. (2018) · Nature Genetics · doi:10.1038/s41588-018-0099-7 · Cited by 8,591
Davey Smith, G., & Ebrahim, S. (2003) · International Journal of Epidemiology · doi:10.1093/ije/dyg070 · Cited by 5,882
Effects of torcetrapib in patients at high risk for coronary events
Barter, P. J., Caulfield, M., Eriksson, M., Grundy, S. M., Kastelein, J. J. P., Komajda, M., Lopez-Sendon, J., Mosca, L., Tardif, J.-C., Waters, D. D., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa0706628 · Cited by 3,139
Effects of extended-release niacin with laropiprant in high-risk patients
The HPS2-THRIVE Collaborative Group (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1300955 · Cited by 1,668
Bias due to participant overlap in two‐sample Mendelian randomization
Burgess, S., Davies, N. M., & Thompson, S. G. (2016) · Genetic Epidemiology · doi:10.1002/gepi.21998 · Cited by 1,624
An atlas of genetic influences on human blood metabolites
The Multiple Tissue Human Expression Resource (MuTHER) Consortium, Shin, S.-Y., Fauman, E. B., Petersen, A.-K., Krumsiek, J., Santos, R., Huang, J., Arnold, M., Erte, I., Forgetta, V., et al. (2014) · Nature Genetics · doi:10.1038/ng.2982 · Cited by 1,515
Polycystic ovary syndrome: etiology, pathogenesis and diagnosis
Goodarzi, M. O., Dumesic, D. A., Chazenbalk, G., & Azziz, R. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.217 · Cited by 1,488
Self-citationAssociation analysis identifies 65 new breast cancer risk loci
Michailidou, K., Lindström, S., Dennis, J., Beesley, J., Hui, S., Kar, S., Lemaçon, A., Soucy, P., Glubb, D. M., Rostamianfar, A., et al. (2017) · Nature · doi:10.1038/nature24284 · Cited by 1,380
Identification and characterization of metabolically benign obesity in humans
Stefan, N. (2008) · Archives of Internal Medicine · doi:10.1001/archinte.168.15.1609 · Cited by 1,049
Using human genetics to understand the disease impacts of testosterone in men and women
The Endometrial Cancer Association Consortium, Ruth, K. S., Day, F. R., Tyrrell, J., Thompson, D. J., Wood, A. R., Mahajan, A., Beaumont, R. N., Wittemans, L., Martin, S., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0751-5 · Cited by 720
Day, F., Karaderi, T., Jones, M. R., Meun, C., He, C., Drong, A., Kraft, P., Lin, N., Huang, H., Broer, L., et al. (2018) · PLOS Genetics · doi:10.1371/journal.pgen.1007813 · Cited by 619
Self-citationThe “metabolically-obese,” normal-weight individual
Ruderman, N. B., Schneider, S. H., & Berchtold, P. (1981) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/34.8.1617 · Cited by 545
The effect of obesity on polycystic ovary syndrome: a systematic review and meta‐analysis
Lim, S. S., Norman, R. J., Davies, M. J., & Moran, L. J. (2013) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01053.x · Cited by 539
Zhang, H., Ahearn, T. U., Lecarpentier, J., Barnes, D. R., Beesley, J., Jiang, X., O’Mara, T. A., Qi, G., Zhao, N., Bolla, M. K., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0609-2 · Cited by 499
Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer
Phelan, C. M., Kuchenbaecker, K. B., Tyrer, J. P., Kar, S., Lawrenson, K., Winham, S. J., Dennis, J., Pirie, A., Riggan, M. J., Chornokur, G., et al. (2017) · Nature Genetics · doi:10.1038/ng.3826 · Cited by 489
Day, F. R., Hinds, D. A., Tung, J. Y., Stolk, L., Styrkarsdottir, U., Saxena, R., Bjonnes, A., Broer, L., Dunger, D. B., Halldorsson, B. V., et al. (2015) · Nature Communications · doi:10.1038/ncomms9464 · Cited by 459
Periodontal systemic associations: review of the evidence
Linden, G. J., Lyons, A., & Scannapieco, F. A. (2013) · Journal of Periodontology · doi:10.1902/jop.2013.1340010 · Cited by 439
Association Between Obesity and Cardiovascular Outcomes
Riaz, H., Khan, M. S., Siddiqi, T. J., Usman, M., Shah, N. P., Goyal, A., Khan, S. S., Mookadam, F., Krasuski, R. A., & Ahmed, H. M. (2018) · JAMA Network Open · doi:10.1001/jamanetworkopen.2018.3788 · Cited by 378
Periodontal systemic associations: review of the evidence
Linden, G. J., Lyons, A., & Scannapieco, F. A. (2013) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.12064 · Cited by 319
Zhao, Y., Fu, L., Li, R., Wang, L., Yan, Y., Liu, N.-N., Zhang, C., Wang, Y., Liu, P., Tu, B.-B., et al. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-153 · Cited by 232
Lawlor, D. A., Ebrahim, S. B. J., & Smith, G. D. (2004) · Diabetologia · doi:10.1007/s00125-003-1310-6 · Cited by 227
Polycystic ovary syndrome and risk of type 2 diabetes, coronary heart disease, and stroke
Zhu, T., Cui, J., & Goodarzi, M. O. (2021) · Diabetes · doi:10.2337/db20-0800 · Cited by 226
Self-citationPerry, J. R. B., Weedon, M. N., Langenberg, C., Jackson, A. U., Lyssenko, V., Sparsø, T., Thorleifsson, G., Grallert, H., Ferrucci, L., Maggio, M., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddp522 · Cited by 217
Oligoanovulation with Polycystic Ovaries But Not Overt Hyperandrogenism
Dewailly, D., Catteau-Jonard, S., Reyss, A.-C., Leroy, M., & Pigny, P. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1054 · Cited by 198
Scott, R. A., Fall, T., Pasko, D., Barker, A., Sharp, S. J., Arriola, L., Balkau, B., Barricarte, A., Barroso, I., Boeing, H., et al. (2014) · Diabetes · doi:10.2337/db14-0319 · Cited by 173
Linsel‐Nitschke, P., Götz, A., Erdmann, J., Brænne, I., Braund, P. S., Hengstenberg, C., Stark, K. J., Fischer, M., Schreiber, S., Mokhtari, N. E. E., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002986 · Cited by 168
Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: a systematic review
Harris, H. R., & Terry, K. L. (2016) · Fertility Research and Practice · doi:10.1186/s40738-016-0029-2 · Cited by 155
Yaghootkar, H., Lotta, L. A., Tyrrell, J., Smit, R. A. J., Jones, S. E., Donnelly, L. A., Beaumont, R. N., Campbell, A., Tuke, M. A., Hayward, C., et al. (2016) · Diabetes · doi:10.2337/db15-1671 · Cited by 151
Brower, M. A., Hai, Y., Jones, M. R., Guo, X., Chen, Y. D. I., Rotter, J. I., Krauss, R. M., Legro, R. S., Azziz, R., & Goodarzi, M. O. (2019) · Human Reproduction · doi:10.1093/humrep/dey343 · Cited by 115
Self-citationYarmolinsky, J., Relton, C. L., Lophatananon, A., Muir, K. R., Menon, U., Gentry‐Maharaj, A., Walther, A., Zheng, J., Fasching, P. A., Zheng, W., et al. (2019) · PLoS Medicine · doi:10.1371/journal.pmed.1002893 · Cited by 107
Martin, S., Cule, M., Basty, N., Tyrrell, J., Beaumont, R. N., Wood, A. R., Frayling, T. M., Sorokin, E. P., Whitcher, B. J., Liu, Y., et al. (2021) · Diabetes · doi:10.2337/db21-0129 · Cited by 105
Ji, Y., Yiorkas, A. M., Frau, F., Mook‐Kanamori, D. O., Staiger, H., Thomas, E. L., Atabaki‐Pasdar, N., Campbell, A., Tyrrell, J., Jones, S. E., et al. (2018) · Diabetes · doi:10.2337/db18-0708 · Cited by 102
The role of AMH in anovulation associated with PCOS: a hypothesis
Homburg, R., & Crawford, G. (2014) · Human Reproduction · doi:10.1093/humrep/deu076 · Cited by 100
Menstrual irregularity and asthma and lung function
Real, F. G., Svanes, C., Omenaas, E. R., Antó, J. M., Plana, E., Janson, C., Jarvis, D., Zemp, E., Wjst, M., Leynaert, B., et al. (2007) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2007.04.041 · Cited by 91
Chang, A. Y., Lalia, A. Z., Jenkins, G. D., Dutta, T., Carter, R. E., Singh, R. J., & Nair, K. S. (2017) · Metabolism · doi:10.1016/j.metabol.2017.03.002 · Cited by 83
Zhao, Y., Xu, Y., Wang, X., Xu, L., Chen, J., Gao, C., Wu, C., Pan, D., Zhang, Q., Zhou, J., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa125 · Cited by 67
Machado, V., Escalda, C., Proença, L., Mendes, J. J., & Botelho, J. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9061961 · Cited by 52
Shorakae, S., Boyle, J. A., & Teede, H. J. (2014) · Internal Medicine Journal · doi:10.1111/imj.12495 · Cited by 48
Zhang, Z., Hong, Y., Chen, M., Tan, N., Liu, S., Nie, X., & Zhou, W. (2020) · Metabolomics · doi:10.1007/s11306-020-1642-y · Cited by 44
Verdiesen, R. M. G., van der Schouw, Y. T., van Gils, C. H., Verschuren, W. M. M., Broekmans, F. J., Borges, M. C., Soares, A. G., Lawlor, D. A., Eliassen, A. H., Kraft, P. L., et al. (2022) · Human Reproduction · doi:10.1093/humrep/deac028 · Cited by 43
Harris, H. R., Cushing‐Haugen, K. L., Webb, P. M., Nagle, C. M., Jordan, S. J., Australian Ovarian Cancer Study Group, Risch, H. A., Rossing, M. A., Doherty, J. A., Goodman, M. T., et al. (2019) · International Journal of Epidemiology · doi:10.1093/ije/dyz113 · Cited by 42
Breast cancer risk in patients with polycystic ovary syndrome: a Mendelian randomization analysis
Wen, Y., Wu, X., Peng, H., Li, C., Jiang, Y., Su, Z., Liang, H., Liu, J., He, J., & Liang, W. (2020) · Breast Cancer Research and Treatment · doi:10.1007/s10549-020-05973-z · Cited by 28
Sun, S., Jiao, M., Han, C., Zhang, Q., Shi, W., Shi, J., & Li, X. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00621 · Cited by 23
Wu, P., Zhang, X., Zhou, P., Zhang, W., Li, D., Lv, M., & Liao, X. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.644101 · Cited by 19
Wu, P.-F., Li, R., Zhang, W., Hu, H., Wang, W., & Lin, Y. (2020) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2020.05.016 · Cited by 18
Adams, C. D., & Boutwell, B. B. (2020) · Scientific Reports · doi:10.1038/s41598-020-69114-8 · Cited by 18
Mendelian randomisation in type 2 diabetes and coronary artery disease
Frayling, T. M., & Harlow, C. E. (2018) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2018.05.010 · Cited by 16
Polycystic ovary syndrome and breast cancer subtypes: a Mendelian randomization study
Zhu, T., Cui, J., & Goodarzi, M. O. (2021) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2021.03.020 · Cited by 16
Self-citationAhn, Y., Lee, H., & Cho, Y. S. (2020) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s281529 · Cited by 11
Polycystic ovary syndrome and lung function: a Mendelian randomization study
van der Plaat, D. A., Minelli, C., Jarvis, D., García‐Aymerich, J., Leynaert, B., & Real, F. G. (2020) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2020.03.003 · Cited by 6
Wu, P., Li, R. Z., Zhang, W., Su, Z. Z., & Lin, Y. H. (2021) · PubMed · doi:10.3967/bes2021.023 · Cited by 5
Research works printed but not linked: 1
- Voight, 2012, Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study, Lancet., 380, 572, 10.1016/S0140-6736(12)60312-2 · DOI · Paper page
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Kautzky-Willer, A., Leutner, M., & Harreiter, J. (2023) · Diabetologia · doi:10.1007/s00125-023-05891-x · Cited by 624
Stener-Victorin, E., Teede, H., Norman, R. J., Legro, R., Goodarzi, M. O., Dokras, A., Laven, J., Hoeger, K., & Piltonen, T. T. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00511-3 · Cited by 495
Self-citationPolycystic ovary syndrome as a metabolic disease
Helvacı, N., & Yıldız, B. O. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-01057-w · Cited by 230
Polycystic ovary syndrome: a “risk-enhancing” factor for cardiovascular disease
Guan, C. S., Zahid, S., Minhas, A. S., Ouyang, P., Vaught, A. “. J., Baker, V. L., & Michos, E. D. (2022) · Fertility and Sterility · doi:10.1016/j.fertnstert.2022.03.009 · Cited by 218
Determining a multimodal aging clock in a cohort of Chinese women
Li, J., Xiong, M., Fu, X.-H., Fan, Y., Dong, C., Sun, X., Zheng, F., Wang, S., Liu, L., Xu, M., et al. (2023) · Med · doi:10.1016/j.medj.2023.06.010 · Cited by 151
Metadata
- Authors
- Zhu, T., & Goodarzi, M. O.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Corresponding author
- Goodarzi, Mark O
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2021-10-20
- Volume
- 107
- Issue
- 3
- Pages
- e899-e911
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC8852214
- OpenAlex
- W3205635727
- Cited by
- 126
- References
- 53
- Citations by year
- 2026: 19 · 2025: 33 · 2024: 41 · 2023: 25 · 2022: 7 · 2021: 1
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Advancing Translational Sciences (UL1TR000124)
- National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (P30-DK063491)
- Eris M. Field Chair in Diabetes Research
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Keywords
- polycystic ovary syndrome, causality, obesity, testosterone, insulin, sex hormone-binding globulin, menopause timing, androgenetic alopecia, depression, estrogen receptor-positive breast cancer, endometrioid ovarian cancer, type 2 diabetes, coronary artery disease, stroke, PCOS prevention
- MeSH terms
- Breast Neoplasms, Depression, Female, Humans, Ovarian Neoplasms, Polycystic Ovary Syndrome, Risk Factors, Causality, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Mendelian Randomization Analysis
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