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Pediatric and adult obesity concerns in female health: a Mendelian randomization study

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Abstract

Purpose

Adulthood and childhood obesity are both associated with reproductive diseases and gynecological cancers in females. However, the causal factors associated with these observations have yet to be identified. Mendelian randomization is a process that is independent of inverse bias and confounding and can act as a random control trial in which genetic groups are settled during meiosis, thus representing an effective tool with which to investigate causality.

Methods

We carried out several Mendelian randomization trials based on the combined genetic scores of 75 adult-associated and 15 childhood-associated body mass index (BMI) single nucleotide polymorphisms (SNPs), databases for several gynecological cancers and reproductive diseases from the UK Biobank (with 194,153 participants), using the traditional inverse-variance weighted (IVW) method as the main method.

Results

Elevated adult-associated BMI scores (odds ratio [OR] = 1.003; 95% confidence interval [CI]: 1.001–1.004) and childhood-associated BMI scores (OR = 1.003; 95% CI: 1.001–1.004) were related to a higher risk of the polycystic ovarian syndrome (PCOS), as determined by the traditional IVW method. The random IVW method further revealed a nominal negative causal association between childhood-associated BMI and subsequent endometriosis (OR = 0.995; 95% CI: 0.991–0.999).

Conclusions

Consistent with observational consequences, our findings indicated that adulthood obesity may play role in the development of PCOS and that childhood obesity can increase the risk of PCOS but may reduce the incidence of endometriosis in later life. Further research is now needed to validate our findings and identify the precise mechanisms involved.

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Data and material availability

Besides the selected SNPs derived from published articles [datasets 1 and 2], we also obtained access to open databases to acquire genetic statistics for diseases outcomes. The data analyzed in this article are available from the UK Biobank, as follows.

https://www.dropbox.com/s/uirk8rmdhmyana7/20001_1041.gwas.imputed_v3.female.tsv.bgz?dl=0 (for cervical cancer)

https://www.dropbox.com/s/a6hxa2xh6ke726y/20001_1040.gwas.imputed_v3.female.tsv.bgz?dl=0 (for endometrial cancer)

https://www.dropbox.com/s/dkgr3ejcxza9f7o/20001_1039.gwas.imputed_v3.female.tsv.bgz?dl=0 (for ovarian cancer)

https://www.dropbox.com/s/4g7f8jpq3dkn6l5/20002_1402.gwas.imputed_v3.female.tsv.bgz?dl=0 (for endometriosis)

https://www.dropbox.com/s/hvpig2a6n4fpsy2/20002_1350.gwas.imputed_v3.female.tsv.bgz?dl=0 (for PCOS)

[dataset 1]: Locke, Adam E et al. “Genetic studies of body mass index yield new insights for obesity biology.” Nature vol. 518,7538 (2015): 197–206. doi:10.1038/nature14177

[dataset 2]: Geng, Tingting et al. “Childhood BMI and Adult Type 2 Diabetes, Coronary Artery Diseases, Chronic Kidney Disease, and Cardiometabolic Traits: A Mendelian Randomization Analysis.” Diabetes care vol. 41,5 (2018): 1089–1096. doi:10.2337/dc17-2141

Code availability

RStudio version 3.6.1.

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Acknowledgements

We would like to extend our gratitude to the authors of the studies cited in this article for their kindness and generosity for allowing the download of reference data for analysis.

Funding

This research was supported by the National Natural Science Foundation of China (Reference: 82088102), the National Natural Science Foundation of China (Reference: 81661128010) and the Fundamental Research Funds for the Central Universities (2021FZZX002-10).

Author contributions

Y.-S.Y. collected data and wrote the paper. Z.Q. analyzed and revised the data. P.-P.L. and H.-F.H. designed the study.

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Authors and Affiliations

  1. The Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

    Yi-Shang Yan, Ping-ping Lv & He-Feng Huang

  2. Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Yi-Shang Yan, Ping-ping Lv & He-Feng Huang

  3. Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China

    Zihao Qu

  4. Orthopedic Research Institute of Zhejiang University, Hangzhou, 310009, Zhejiang, China

    Zihao Qu

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  1. Yi-Shang Yan
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Corresponding author

Correspondence to He-Feng Huang.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate and publication

We did not require ethical approval from an ethics committee, or a checklist referenced by the Equator Network, because our study did not involve human and animal research, or observational studies. We performed Mendelian randomization analysis on published data and open databases to investigate the causal associations between exposures and outcomes. All of the cited projects and datasets were approved by relevant ethics committees associated with the corresponding published articles.

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These authors contributed equally: Yi-Shang Yan, Zihao Qu

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Yan, YS., Qu, Z., Lv, Pp. et al. Pediatric and adult obesity concerns in female health: a Mendelian randomization study. Endocrine 75, 400–408 (2022). https://doi.org/10.1007/s12020-021-02867-y

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