Author(s)

Ma Min ^1,2, Li Meihe ³, Mu Siqi ¹, Dang Huimin ²

Affiliation(s)

¹ Shaanxi University of Chinese Medicine, Xianyang, China
² Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi 'an, China
³ The First Affiliated Hospital of Xi 'an Jiaotong University, Xi'an, China

Corresponding Author

ABSTRACT

PCOS (polycystic ovary syndrome, PCOS) is a complex disease involving endocrine and metabolism, but its specific etiology and risk factors are not clear. Mendel randomization is to use instrumental variables to verify the causal relationship between risk factors and outcomes. This method can effectively reduce the interference of confounding factors and reverse causality. In recent years, Mendel's randomization research method has been widely used in the etiology research of various diseases. This paper reviews this method and its application progress in PCOS research. The current research results support the causal relationship between PCOS and breast cancer, low-grade serous ovarian cancer, intestinal flora, circulating metabolites, lifestyle and so on. Although many studies have certain limitations, they provide new ideas for the causal relationship research of PCOS, and also play a potential guiding role in the treatment and intervention of the disease.

KEYWORDS

CITE THIS PAPER

Ma Min, Li Meihe, Mu Siqi, Dang Huimin. Application of Mendel Randomization in Etiology Study of Polycystic Ovary Syndrome. MEDS Clinical Medicine (2024) Vol. 5: 145-150. DOI: http://dx.doi.org/10.23977/medsc.2024.050520.

REFERENCES

[1] Héctor F. Escobar-Morreale.Polycystic ovary syndrome: Definition, aetiology, diagnosis and treatment[J].Nature Reviews Endocrinology, 2018, 14(5).DOI:10.1038/nrendo.2018.24.
[2] Patel, Seema. Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy[J].Journal of Steroid Biochemistry & Molecular Biology, 2018:S0960076018300396.DOI:10.1016/j.jsbmb.2018.04.008.
[3] Kong F S , Feng J , Yao J P ,et al.Dysregulated RNA editing ofEIF2AK2in polycystic ovary syndrome: clinical relevance and functional implications[J].BMC Medicine, 2024, 22(1).DOI:10.1186/s12916-024-03434-8.
[4] Patel, Seema. Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy[J].Journal of Steroid Biochemistry & Molecular Biology, 2018:S0960076018300396.DOI:10.1016/j.jsbmb.2018.04.008.
[5] Sekula P , Del G M F , Pattaro C ,et al.Mendelian Randomization as an Approach to Assess Causality Using Observational Data[J].Journal of the American Society of Nephrology, 2016:3253-3265.DOI: 10.1681/ASN. 2016010098.
[6] Wang L N, Zhang Z. Mendelian randomization approach, used for causal inferences][J]. Chinese Journal of Epidemiology, 2017, 38(4):547-552.DOI:10.3760/cma.j.issn.0254-6450.2017.04.027.
[7] Zhou Chengcheng, Pang Ying, He Yi, et al. Mendelian Randomized Analysis of Depression and Breast Cancer Risk [J]. chinese mental health journal, 2023, 37(6):471-478.
[8] Winslw, U.C., Nordestgaard B G, Afzal S. The plasma level of 25‐ hydroxyvitamin D is high, and the risk of non-melanoma skin cancer is high: a Mendelian randomized study involving 97,849 subjects [J]. British Journal of Dermatology, 2018,178 (6): E455.
[9] Li Lanxin, Xu Zhe, Gou Lan, et al. Bibliometrics and visual analysis of Mendel's randomized research in the field of ischemic stroke [J]. China Journal of Stroke, 2023,18(03):273-280.
[10] Xu Yaxiong, Li Huiqing, Qin Zhiquan. Mendel randomized analysis of the causal relationship between polycystic ovary syndrome and female malignant tumor [J]. Modern Preventive Medicine, 2023,50(23):4253-4259+4265.
[11] Han Xinyu, Wu Tianqiang, Feng Xiaoling. Mendel randomized study on the causal relationship between hypothyroidism and polycystic ovary syndrome [J]. Modern Preventive Medicine, 2023,50(16):2881-2884+2897.
[12] Zhao, Zhendan et al. “Thyroid function and polycystic ovary syndrome: a Mendelian randomization study.” Frontiers in endocrinology vol. 15 1364157. 22 Mar. 2024, doi:10.3389/fendo.2024.1364157.
[13] Li, Miao et al. "The gut microbial composition in polycystic ovary syndrome with hyperandrogenemia and its association with steroid hormones." Frontiers in cell and developmental biology vol. 121384233. 30 May. 2024.
[14] Li, Jing-Wei et al. "Gut microbiota and risk of polycystic ovary syndrome: Insights from Mendelian randomization." Heliyon vol. 9,12 e22155. 21 Nov. 2023, doi:10.1016/j.heliyon.2023.e22155.
[15] Wang J, Fiori PL, Capobianco G, et al Gut microbiota and polycystic ovary syndrome, focus on genetic associations: a bidirectional Mendelian randomization study. Front Endocrinol (Lausanne). 2024;15:1275419. Published 2024 Jan 22.
[16] Liang Y, Zeng W, Hou T, et al. Gut microbiome and reproductive endocrine diseases: a Mendelian randomization study. Front Endocrinol (Lausanne). 2023;14:1164186. Published 2023 Aug 4. doi:10.3389/fendo.2023.1164186.
[17] Li HWR, Brereton RE, Anderson RA, et al.. Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovaryyndrome. Metabolism 2011;60: 1475–1481. 10.1016/j.metabol.2011.03.002.
[18] Shan C, Zhu YC, Yu J, Zhang Y, Wang YY, Lu N, Cai J, Liu W, Tao T. Low Serum 25-Hydroxyvitamin D Levels Are Associated With Hyperandrogenemia in Polycystic Ovary Syndrome: A Cross-Sectional Study. Front Endocrinol (Lausanne). 2022 May 2;13:894935. doi: 10.3389/fendo.2022.894935. 
[19] Shen JY, Xu L, Ding Y, etal. Effect of vitamin supplementation on polycystic ovary syndrome and key pathways implicated in its development: A Mendelian randomization study. World J Clin Cases. 2023 Aug 16;11(23):5468-5478. doi: 10.12998/wjcc.v11.i23.5468. 
[20] Handelsman, David J, and Susan R Davis. "Measuring serum testosterone in women.Thelancet.Diabetes& endocrinology, S2213-8587(24)00134-7.22May.2024,doi:10.1016/S2213-8587(24)00134-7.
[21] Zhao, Benzheng etal. "Genetically predicted serum testosterone and risk of gynecological disorders: a Mendelian randomization study." Frontiers in endocrinology vol. 14 1161356. 21 Nov. 2023, doi:10.3389/fendo.2023.1161356.
[22] Brower, M A et al. "Bidirectional Mendelian randomization to explore the causal relationships between body mass index and polycystic ovary syndrome." Human reproduction (Oxford, England) vol. 34,1 (2019): 127-136. doi:10.1093/ humrep/dey343.
[23] Zeng Haijing, Liu Yaqi, Zhang Xuehong. Exploring the relationship between obesity and polycystic ovary syndrome based on Mendel randomization [J]. Journal of Lanzhou University (Medical Edition), 2023,49(05):57-61.
[24] Tao, Yingli et al. "Genetically Predicted Cigarette Smoking in Relation to Risk of Polycystic Ovary Syndrome." Clinical epidemiologyvol.13527-532. 2 Jul. 2021, doi:10.2147/CLEP.S311785.
[25] Zhao, Yuheng et al. "Causal relationships between modifiable risk factors and polycystic ovary syndrome: a comprehensive Mendelian randomization study." Frontiers in endocrinology vol. 15 1348368. 8 May. 2024, doi: 10.3389/ fendo.2024.1348368.
[26] Depression and Other Common Mental Disorders. [(accessed on 6 February2024)]. Availableonline: https://www.who.int/publications/i/item/depression-global-health-estimates.
[27] Ling, Shuyi et al. "Epidemiologic and genetic associations of female reproductive disorders with depression or dysthymia: a Mendelian randomization study." Scientific reports vol. 14,15984. 12 Mar. 2024, doi:10.1038/s41598-024 -55993-8.
[28] Jiang, X et al. "Is there a shared genetic basis and causal relationship between polycystic ovary syndrome and psychiatric disorders: evidence from a comprehensive genetic analysis." Human reproduction(Oxford, England)vol.36, 8(2021):2382-2391.doi:10.1093/humrep/deab119.
[29] Ge Hang, Chang Hui, Wang Yu, et al. Relationship between menarche age and TCM syndrome types and reproductive endocrine characteristics of infertile women with polycystic ovary syndrome in childbearing age [J]. Chinese Journal of Traditional Chinese Medicine, 2024,39(02):962-967.
[30] Ma, Yuanlin et al. "Age at menarche and polycystic ovary syndrome: A Mendelian randomization study." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics vol. 162,3 (2023): 1050-1056. doi:10.1002/ijgo.14820.

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