Age at menarche and ischemic heart disease: An update mendelian randomization study

Abstract

Background: Although earlier menarche age has been associated with ischemic heart disease in previous observational studies, the relationship’s causation has not been shown. Through two-sample Mendelian randomization (MR), we were able to define the causal connection.Methods: We performed Mendelian Randomization (MR) analysis to explore the associations between genetically predicted AAM and IHD. Summary-level databases for exposure and outcome were selected from the MR-Base database (https://gwas.mrcieu.ac.uk/). Single-nucleotide polymorphisms (SNPs) connected to AAM at genome-wide significance level (p < 5 × 10−8) were considered as instrumental variables (IVs). We used four methods to pool MR estimates, including fixed-effects inverse variance weighting (fe-IVW), multiplicative random-effects inverse variance weighting (mre-IVW), weighted median (WM), and MR-Egger regression methods. Sensitivity analyses were performed to evaluate the robustness of the results. PhenoScanner searches and Multivariable Mendelian randomization (MVMR) analysis was used for assessing confounders.Results: 117 SNPs significantly correlated with AAM were screened as instruments, the results of three main methods showed that genetically earlier AAM may have a causal effect on the higher risk of IHD (fe-IVW: OR = 0.80, 95% CI: 0.72–0.88, p < 0.001; mre-IVW: OR = 0.80, 95% CI: 0.70–0.90, p < 0.001; WE: OR = 0.79, 95% CI: 0.66–0.93, p = 0.006). These results were consistent across sensitivity analyses. MR analysis revealed that there was still a relationship between AAM and IHD even when pleiotropic SNPs of confounders were removed employing PhenoScanner searches. In MVMR, the significant association remained after adjusting for biological sex, but it was attenuated with adjustment of body mass index including childhood and adult.Conclusion: Our MR analysis revealed a substantial genetically determined confounder-mediated relationship between an increase in genetically predicted AAM and a lower risk of IHD. By addressing the intervention of body mass index, the risk of IHD may be lowered.

The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis

“…In the IEU open GWAS platform, the GWAS ID corresponding to EC, GC, CRC, HCC, BTC, and PC was “bbj-a-117,” “bbj-a-119,” “bbj-a-107,” “bbj-a-158,” “bbj-a-92,” and “bbj-a-140,” respectively. During the process of extracting SNPs linked to the exposure from the outcome, any SNPs lacking pertinent details in the outcome were excluded 26 .…”

Mitochondrial DNA copy number and cancer risks: A comprehensive Mendelian randomization analysis

“…In the IEU open GWAS project, the GWAS IDs corresponding to pan‐cancer and breast, lung, prostate, skin, colorectal, gastric, liver, cervical uteri, esophageal, thyroid, bladder, pancreas, kidney, corpus uteri, lip and oral cavity, ovary, brain, larynx, testis, and anus cancers were “finn‐b‐C3_CANCER,” “finn‐b‐C3_BREAST,” “finn‐b‐C3_BRONCHUS_LUNG,” “finn‐b‐C3_PROSTATE,” “finn‐b‐C3_OTHER_SKIN,” “finn‐b‐C3_COLORECTAL,” “finn‐b‐C3_STOMACH,” “finn‐b‐C3_LIVER_INTRAHEPATIC_BILE_DUCTS,” “finn‐b‐C3_CERVIX_UTERI,” “finn‐b‐C3_OESOPHAGUS,” “finn‐b‐C3_THYROID_GLAND,” “finn‐b‐C3_BLADDER,” “finn‐b‐C3_PANCREAS,” “finn‐b‐C3_KIDNEY_NOTRENALPELVIS,” “finn‐b‐C3_CORPUS_UTERI,” “finn‐b‐C3_LIP_ORAL_PHARYNX,” “finn‐b‐C3_OVARY,” “finn‐b‐C3_BRAIN,” “finn‐b‐C3_LARYNX,” “finn‐b‐C3_TESTIS,” and “finn‐b‐C3_ANUS_ANALCANAL,” respectively. During the extraction of SNPs associated with the exposure from the outcome, any SNPs without relevant information in the outcome were eliminated 38 …”

“…During the extraction of SNPs associated with the exposure from the outcome, any SNPs without relevant information in the outcome were eliminated. 38 Furthermore, participant overlap in MR analysis can increase type I errors. Although the three sets of IVs were obtained from three publicly available articles, it is important to note that all three studies utilized partial data from the UKB database.…”

Unraveling the Causal Relationship between Blood Metabolites and Acne: A Metabolomic Mendelian Randomization Study

“…To address potential confounding variables, we thoroughly examined the instrumental variables (IVs) for metabolites on the Phenoscanner V2 platform. We assessed the associations between each single nucleotide polymorphism (SNP) and established risk factors for acne, and if any signi cant correlations were found, these SNPs were excluded from further MR analysis to ensure result integrity 17 . Multivariable Mendelian randomization (MVMR) analysis was then employed to evaluate the causal relationships between multiple exposures and acne.…”