Age at first birth, age at menopause, and risk of ovarian cyst: a two-sample Mendelian randomization study
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PROVIDER: S-EPMC10794498 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundGrowing evidence suggests that female reproductive factors, like age at first birth (AFB), may play a potential role in the progression of lung cancer (LC). However, previous studies are susceptible to confounding factors, inadequate attention to variation by histology or reverse causality. Few studies have comprehensively evaluated their association and the causal effect remains unclear.MethodsWe aimed to determine whether AFB is causally correlated with the risk of LC, by means of utilizing aggregated data from the large genome-wide association studies conducted on AFB (251,151 individuals) and data of LC from International Lung and Cancer Consortium (ILCCO, 11,348 cases and 15,861 controls). We used 10 AFB-related single nucleotide polymorphisms as instrument variables and applied several two-sample Mendelian randomization (MR) methods. Secondary results according to different histological subtypes of lung cancer were also implemented.ResultsConventional inverse-variance weighted method indicated that genetic predisposition towards number unit (1 year) increase of AFB was associated with a 18% lower risk of LC [odds ratio (OR) =0.82, 95% confidence interval (CI): 0.69-0.97; P=0.029]. When results were examined by histotypes, an inverse association was observed between genetically predisposed number unit (1 year) increase of AFB and lung adenocarcinoma (OR =0.75, 95% CI: 0.59-0.97, P=0.017) but not with squamous cell lung cancer (OR =0.77, 95% CI: 0.57-1.05, P=0.103). The results demonstrated no association between number unit decrease of AFB and LC. Pleiotropy was not presented through sensitivity analyses including MR pleiotropy residual sum and outlier test (P=0.412). Genetic predisposition towards older AFB was additionally associated with longer years of schooling (OR =1.12, 95% CI: 1.08-1.16, P<0.001), lower body mass index (OR =0.93, 95% CI: 0.88-0.98, P=0.004) and less alcohol consumption (OR =0.99, 95% CI: 0.99-1.00, P=0.004).ConclusionsOur study suggested that older AFB was a causal protective factor in the progression of LC. Further studies elucidating the potential mechanisms are needed.
| S-EPMC8107761 | biostudies-literature
Project description:BackgroundPrevious observational research has documented an association between age at first childbirth (AFB) and postpartum depression (PPD). However, the causal relationship remains unclear. This study aimed to assess the causal effects of AFB on PPD using a two-sample Mendelian randomization (MR) analysis.MethodsThree sets of instrumental variables were obtained from the United Kingdom Biobank (UK Biobank), Neale Lab consortium and a meta-analysis of genome-wide association studies (GWAS). Single-nucleotide polymorphisms (SNPs) associated with the PPD phenotype were obtained from the Finngen consortium, which included 13,657 cases and 236,178 controls. Inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger methods to evaluate causal effects. Heterogeneity was assessed using Cochran's Q test and funnel plots. Horizontal pleiotropy and sensitivity were assessed using the MR-Egger intercept test and "leave-one-out" analysis, respectively. Further meta-analysis was performed to validate the robustness of this relationship. Additionally, the potential mediating effects of risk factors associated with PPD were analyzed.ResultsStrong causal effects between AFB and PPD was found in both IVW and weighted median methods, which was further supported by meta-analysis (IVW, odds ratio [OR] 0.59 [95% confidence interval (CI) 0.36-0.96, p = 0.03]; weighted median, OR 0.59 [95% CI 0.37-0.95, p = 0.03]). The power of the MR supports the robustness of the findings. Heterogeneity or horizontal pleiotropy was not observed. Major depressive disorders, family income levels, and marital stress were identified as potential mediating factors in the causal relationships.ConclusionResults of MR analysis supported the causal effect of increased AFB in reducing the risk for PPD.
| S-EPMC10543215 | biostudies-literature
Project description:ObjectiveExplore the causal relationship between the ovarian cyst and depression using a two-sample Mendelian randomization approach (MR).MethodsBased on data pooled from genome-wide association studies, genetic variants of the ovarian cyst and depression were selected as instrumental variables, as well as the Mendelian randomization analysis was conducted using inverse variance weighted (IVW) as the main analysis method and MR-Egger regression analysis, MR-PRESSO and other sensitivity analysis methods as supplements.ResultsThe IVW analysis showed a direct causal association between ovarian cysts and depression (OR=1.040; 95% CI: 1.003, 1.078; p=0.031). Meantime, there was a causal effect of genetically predicted depression on ovarian cysts (OR=1.327.; 95% CI: 1.197, 1.470; p<0.001). Sensitivity analyses such as MR-Egger regression analysis and MR-PRESSO indicated that the IVW results were robust and reliable.ConclusionThis study suggested since ovarian cysts and female depression are mutually causal, the comorbidity of ovarian cysts and depression in women should be actively attended to and given appropriate prevention and treatment besides the diagnosis and treatment of depression or ovarian cysts.
| S-EPMC10644873 | biostudies-literature
Project description:ObjectivesTo determine whether the age at menarche (AAM) and the age at menopause (ANM) are causally related to the development of sepsis.MethodsWe performed a two-sample Mendelian randomization (MR) analysis by utilizing summary statistics from genome-wide association study (GWAS) datasets for both the exposure and outcome variables. Single nucleotide polymorphisms (SNPs) that exhibited significant associations with AAM and ANM were chosen as instrumental variables to estimate the causal effects on sepsis. Our study employed a variety of methods, including MR-Egger regression, weighted median estimation, inverse variance weighting, a simple model, and a weighted model. Odds ratios (ORs) along with their corresponding 95% confidence intervals (CIs) were used as the primary indicators for assessing causality. Furthermore, we conducted sensitivity analyses to explore the presence of genetic heterogeneity and validate the robustness of the tools employed.ResultOur analysis revealed a significant negative causal relationship between AAM and the risk of sepsis (IVW: OR = 0.870, 95% CI = 0.793-0.955, P = 0.003). However, our Mendelian randomization (MR) analysis did not yield sufficient evidence to support a causal link between ANM and sepsis (IVW: OR = 0.987, 95% CI = 0.971-1.004, P = 0.129).ConclusionsOur findings suggest that an earlier AAM may be associated with an increased risk of sepsis. However, we did not find sufficient evidence to support a causal relationship between ANM and sepsis.
| S-EPMC10849219 | biostudies-literature
Project description: Not available
| S-EPMC10713650 | biostudies-literature
Project description:BackgroundThere is increasing evidence that sex hormones are involved in the development of lung cancer, but the correlation between the reproductive behavior that changes sex hormone levels and lung cancer is not yet clear. Many previous studies have investigated the association between reproductive factors and lung cancer risk, but the results have been inconsistent. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to explore the potential relationship between age at first sexual intercourse (AFS), age at menarche, and age at menopause, and lung cancer.MethodsWe performed a MR analysis of the data from the genome-wide association study (GWAS) of European ancestry to evaluate the independent effects of three reproductive behaviors on lung cancer overall (LUCA), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and small cell lung cancer (SCLC). We mainly used the inverse-variance weighting method for the MR analysis. Sensitivity was determined by a MR-pleiotropy residual sum and outlier analysis, a weighted median analysis, a MR-Egger analysis, and a leave-one-out analysis.ResultsThe MR analysis results revealed that older AFS had a causal relationship with LUCA [odds ratio (OR) =0.6283, 95% confidence interval (CI): 0.4959-0.7961, P=0.0001), LUAD (OR =0.7042, 95% CI: 0.4967-0.9984, P=0.049), and LUSC (OR =0.6231, 95% CI: 0.4386-0.8853, P=0.0083).ConclusionsOur results revealed a causal relationship between older AFS and a lower risk of lung cancer. Our findings emphasize the importance of providing sex education, as early sexual intercourse may have undesirable effects. In addition, early psychological treatment is also essential.
| S-EPMC11304150 | biostudies-literature
Project description:Menopause marks the end of the reproductive phase of life. Based on epidemiological studies, abnormal age at natural menopause (ANM) is thought to contribute to a number of adverse outcomes, such as osteoporosis, cardiovascular disease, and cancer. However, the causality of these associations remains unclear. A powerful epidemiological method known as Mendelian randomization (MR) can be used to clarify the causality between ANM and other diseases or traits. The present review describes MR studies that included ANM as an exposure, outcome and mediator. The findings of MR analyses on ANM have revealed that higher body mass index, poor educational level, early age at menarche, early age at first live birth, early age at first sexual intercourse, and autoimmune thyroid disease appear to be involved in early ANM etiology. The etiology of late ANM appears to be influenced by higher free thyroxine 4 and methylene tetrahydrofolate reductase gene mutations. Furthermore, early ANM has been found to be causally associated with an increased risk of osteoporosis, fracture, type 2 diabetes mellitus, glycosylated hemoglobin, and the homeostasis model of insulin resistance level. In addition, late ANM has been found to be causally associated with an increased systolic blood pressure, higher risk of breast cancer, endometrial cancer, endometrioid ovarian carcinoma, lung cancer, longevity, airflow obstruction, and lower risk of Parkinson's disease. ANM is also a mediator for breast cancer caused by birth weight and childhood body size. However, due to the different instrumental variables used, some results of studies are inconsistent. Future studies with more valid genetic variants are needed for traits with discrepancies between MRs or between MR and other types of epidemiological studies.
| S-EPMC10520463 | biostudies-literature
Project description:Our study aims to investigate whether there is evidence for a causal relationship between self-reported myopia and age-related cataract (ARC). A two-sample Mendelian randomization study was performed to identify the causal associations of self-reported myopia with ARC. We used summary-level genetic association data from the MR-Base (Mendelian Randomization-Base) platform on self-reported myopia and ARC. 26 single-nucleotide polymorphisms (SNPs) associated with self-reported myopia were used as instrumental variables. The inverse-variance weighted (IVW) method was applied to perform the primary analysis, and the weighted median method, MR-Egger regression, and Maximum likelihood methods were selected as supplementary analysis. To ensure the reliability of the results, we also performed the sensitivity analysis and MR-PRESSO analysis to assess the heterogeneity and horizontal pleiotropy. Our results provided evidence for a causal effect of self-reported myopia on ARC risk (IVW: OR 10.657, 95% CI (3.175-35.776), P < 0.001). The results of the weighted median method, MR-Egger regression and Maximum likelihood methods were consistent with the result of the IVW method. No evidence of heterogeneity and horizontal pleiotropy was found by the sensitivity analysis and MR-PRESSO analysis. This study demonstrated that self-reported myopia increases the risk of ARC and provided evidence to support public health interventions to prevent the onset and progress of myopia and develop new therapeutic strategies for myopia. Further large-scale prospective studies are required to validate our findings.
| S-EPMC11909268 | biostudies-literature
Project description: Not available
| S-EPMC10916238 | biostudies-literature
Project description:In previous observational studies, physical activity may have an impact on the age at menopause (ANM), potentially delaying or advancing the onset of menopause. However, the causal relationship between physical activity and age at menopause remains unclear. Therefore, we designed a 2-sample Mendelian randomization (MR) and mediation MR study to explore the causal relationship between physical activity and ANM and to identify potential mediating factors such as BMI, insomnia, hypertension and hyperglycemia. We investigated the causal link between physical activity and age at menopause using 2-sample Mendelian randomization (MR) and tested for potential mediators using 2-step MR. Our approach includes IVW and other MR methods and uses a variety of sensitivity tests to verify the robustness of the results. In 2-sample MR analysis, moderate physical activity was associated with delayed age at menopause (β = 0.64, 95% CI = [0.02-1.26], P = .04), but there was no evidence of a causal relationship between vigorous physical activity and age at menopause (P = .68).In contrast, a 2-step MR method showed that body mass index (BMI) mediated the effects of physical activity and delayed age at menopause (proportion mediated, 4.9%, 95% CI = 0.8 to 8%; P = .02), whereas the mediating effects of insomnia, hypertension and hyperglycemia were not significant. Our study shows that moderate physical activity can delay the age of menopause and is informative for the prevention of ovarian failure and the maintenance of women's reproductive health.
| S-EPMC11813050 | biostudies-literature