Age at menarche and ischemic heart disease: An update mendelian randomization study
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...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.942861/full |
| _version_ | 1811192726860857344 |
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| author | Jing Chen Heng Chen Qiaozhen Zhu Qiannan Liu Yan Zhou Lan Li Lan Li Yan Wang |
| author_facet | Jing Chen Heng Chen Qiaozhen Zhu Qiannan Liu Yan Zhou Lan Li Lan Li Yan Wang |
| author_sort | Jing Chen |
| collection | DOAJ |
| description | 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. |
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| language | English |
| last_indexed | 2024-04-11T23:57:11Z |
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| spelling | doaj.art-2f0bd730b15a42cca151f19bc6534b0f2022-12-22T03:56:20ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-11-011310.3389/fgene.2022.942861942861Age at menarche and ischemic heart disease: An update mendelian randomization studyJing Chen0Heng Chen1Qiaozhen Zhu2Qiannan Liu3Yan Zhou4Lan Li5Lan Li6Yan Wang7The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaClinical Medical School, Henan University, Kaifeng, ChinaThe First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, ChinaThe First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, ChinaThe First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Pediatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Pediatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fgene.2022.942861/fullage at menarcheischemic heart diseasemendelian randomizationcausalitysingle nucleotide polymorphisms |
| spellingShingle | Jing Chen Heng Chen Qiaozhen Zhu Qiannan Liu Yan Zhou Lan Li Lan Li Yan Wang Age at menarche and ischemic heart disease: An update mendelian randomization study Frontiers in Genetics age at menarche ischemic heart disease mendelian randomization causality single nucleotide polymorphisms |
| title | Age at menarche and ischemic heart disease: An update mendelian randomization study |
| title_full | Age at menarche and ischemic heart disease: An update mendelian randomization study |
| title_fullStr | Age at menarche and ischemic heart disease: An update mendelian randomization study |
| title_full_unstemmed | Age at menarche and ischemic heart disease: An update mendelian randomization study |
| title_short | Age at menarche and ischemic heart disease: An update mendelian randomization study |
| title_sort | age at menarche and ischemic heart disease an update mendelian randomization study |
| topic | age at menarche ischemic heart disease mendelian randomization causality single nucleotide polymorphisms |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.942861/full |
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