Spontaneous Abortion and Myocardial Infarction: A Mendelian Randomization Investigation and Transcriptomic Analysis.

Abstract

Background: A link has been found between spontaneous abortion (SA) and myocardial infarction (MI). However, there is still a lack of comprehensive knowledge regarding the genetic links and biological mechanisms between SA and MI. An investigation of the causal association between SA and MI, along with the associated signaling networks, was conducted using univariate Mendelian randomization (MR) and transcriptome analysis.

Methods: Data from genome-wide association studies (GWAS) for SA and MI were analyzed using the FinnGen consortium database. To assess the causality between SA and MI, various methods were employed including inverse-variance-weighted (IVW), weighted median, simple mode, and weighted mode analyses. Sensitivity analysis was conducted using heterogeneity, pleiotropy, and the Leave-One-Out (LOO) approach. Transcriptomic analysis of the GSE60993 dataset was performed to identify differentially expressed genes (DEGs) associated with single nucleotide polymorphisms (SNPs). Following this, two bioinformatics analyses were carried out.

Results: Based on IVW results, SA was found to be causally associated with MI (OR = 1.095, 95%CI 1.012-1.186). Sensitivity analysis was subsequently conducted to validate the robustness of our findings. Through differential analysis, three key genes - GNAQ, ELP3, and TES - were identified as closely linked to processes related to ribosome biogenesis, DNA replication, and congenital immune deficiency. Furthermore, strong correlations were observed with various immunologic gene sets, including the Major Histocompatibility Complex (MHC), immunoactivators, and immunosuppressors.

Conclusion: This study reveals a robust causal relationship between SA and MI, highlighting genetic and immunological pathways that could inform future research and therapeutic approaches.