Early menopause is associated with circumstances at birth, poor cognitive abilities and modifiable behavioral factors, reports a study published in BMCWomensHealth
We include a wide range of prospectively collected risk factors ensuring in all models that known and measured confounders are accounted for, but potential biases resulting from unobserved confounding is inevitable.
Our analysis investigates common risk factors for women born 12 years apart which may obscure cohort-specific relationships. We use a combined study because of the comparable study designs and measures but acknowledge the potential for bias in the harmonized data that may result from combining data from different studies which may in turn affect the generalizability of our findings.
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Mendelian randomization analysis of factors related to ovulation and reproductive function and endometrial cancer risk - BMC MedicineBackground Observational epidemiological studies suggest a link between several factors related to ovulation and reproductive function and endometrial cancer (EC) risk; however, it is not clear whether these relationships are causal, and whether the risk factors act independently of each other. The aim of this study was to investigate putative causal relationships between the number of live births, age at last live birth, and years ovulating and EC risk. Methods We conducted a series of observational analyses to investigate various risk factors and EC risk in the UK Biobank (UKBB). Additionally, multivariate analysis was performed to elucidate the relationship between the number of live births, age at last live birth, and years ovulating and other related factors such as age at natural menopause, age at menarche, and body mass index (BMI). Secondly, we used Mendelian randomization (MR) to assess if these observed relationships were causal. Genome-wide significant single nucleotide polymorphisms (SNPs) were extracted from previous studies of woman’s number of live births, age at menopause and menarche, and BMI. We conducted a genome-wide association analysis using the UKBB to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth. Results We found evidence for a causal effect of the number of live births (inverse variance weighted (IVW) odds ratio (OR): 0.537, p = 0.006), the number of years ovulating (IVW OR: 1.051, p = 0.014), in addition to the known risk factors BMI, age at menarche, and age at menopause on EC risk in the univariate MR analyses. Due to the close relationships between these factors, we followed up with multivariable MR (MVMR) analysis. Results from the MVMR analysis showed that number of live births had a causal effect on EC risk (OR: 0.783, p=0.036) independent of BMI, age at menarche and age at menopause. Conclusions MVMR analysis showed that the number of live births causally reduced the ri
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