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Goal to investigate the possible causal association between hypothyroidism and unfavorable pregnancy outcomes through the use of bioinformatics and Mendelian randomization (MR). Methods: We used Mendelian randomization (MR) analyses using single nucleotide polymorphism (SNP) sites as instrumental variables to infer causal associations between exposures and outcomes. The inverse variance weighting method was primarily used in the analysis. Heterogeneity and horizontal multiplicity tests were also conducted to evaluate the results' robustness and the degree of causality. Lastly, preliminary bioinformatics analyses were conducted to investigate the underlying biological mechanisms. Results: The resultant variance inverse weighting method found that hypothyroidism increased the risk of developing gestational hypertension (OR=1.054, 95% CI: 1.002– 1.110 P=0.042) and poor foetal growth (OR=1.081, 95% CI:1.005– 1.162 P=0.035). Heterogeneity tests, multiplicity tests and leave-one-out sensitivity analyses did not reveal any heterogeneity or multiplicity effects in the estimated effects of these three exposure factors on the risk of ovarian dysfunction. Conclusion: Our research establishes genetically the causal relationship between pregnancy-related hypertension, hypothyroidism, and poor fetal growth—a relationship that could be linked to endosomal and cellular transport. [ABSTRACT FROM AUTHOR]

This paper aims to explore the causal relationship between genetic proxies for lipid-lowering drugs and breast and endometrial cancers using drug-target Mendelian randomization (MR). Methods: Analyses were mainly performed using inverse variance weighted (IVW), heterogeneity and horizontal pleiotropy tests, and sensitivity analysis to assess the robustness of the results and causal relationship. Results: HMGCR, APOB, and NPC1L1 increased the risk of breast cancer, LPL increased the risk of endometrial cancer, and APOC3 decreased the risk of breast and endometrial cancer. No heterogeneity or horizontal pleiotropy was detected, and nor was there any evidence of an association between other lipid-lowering drugs and breast and endometrial cancer. Conclusion: Our study demonstrated genetically that HMGCR inhibition, APOB inhibition, and NPC1L1 inhibition decrease the risk of breast cancer, LPL agonist increases the risk of endometrial cancer, and APOC3 inhibition decreases the risk of breast cancer and endometrial cancer, and these findings provide genetic insights into the potential risks of lipid-lowering drug therapy. [ABSTRACT FROM AUTHOR]

Background: Observational studies have revealed associations between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. However, these studies are susceptible to unavoidable confounding factors, leading to ongoing debates regarding their conclusions and making causal relationships challenging to infer. In light of these challenges, Mendelian randomization was employed in this study to investigate the causal relationships between birth weight, childhood obesity, age at menarche, and ovarian dysfunction., Methods: This study employed a two-sample Mendelian randomization approach using genetic variation as instrumental variables to investigate causal relationships. Genetic variation data were sourced from summary data of genome-wide association studies in European populations. Instrumental variables were selected based on the principles of Mendel's three assumptions. The study utilized the inverse variance weighted method to assess the relationships between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. Supplementary analyses were conducted using MR-Egger regression, the weighted median method, and the weighted median mode to complement the IVW results. Furthermore, the study conducted heterogeneity, horizontal pleiotropy, and sensitivity analyses to evaluate the robustness of the results., Results: Based on the inverse variance weighted method, it was found that there exists a causal relationship between childhood obesity (OR = 1.378, 95% CI: 1.113∼1.705, p = 0.003), age at menarche (OR = 0.639, 95% CI: 0.468∼0.871, p = 0.005), and ovarian dysfunction, while no causal relationship was observed between birth weight and ovarian dysfunction. Heterogeneity tests, multiplicity tests, and leave-one-out sensitivity analyses did not detect any heterogeneity or multiplicity effects in the estimated impact of these three exposure factors on the risk of ovarian dysfunction., Conclusions: This study represents the first evidence suggesting a potential causal relationship between childhood obesity, age at menarche, and ovarian dysfunction. Childhood obesity was found to increase the risk of ovarian dysfunction, while a later age at menarche was associated with a reduced risk of ovarian dysfunction., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Dang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)