Key result
Genome- and exome-wide analysis identifies ~9 shared genes linking MI and severe mental disorders.
Why the study?
Myocardial infarction and severe mental disorders are prevalent comorbid conditions with high mortality, but the contributions of common and rare genetic variants to their comorbidity remain unclear.
Observational (n=200,000)
Yes
This study maps the shared common and rare genetic architecture between myocardial infarction and severe mental disorders, offering novel insights into the biological pathways driving their frequent comorbidity.
Shared genetic signals in MI and severe mental illness are hypothesis-generating; leaves open any role in risk stratification or therapy.
Background: Myocardial Infarction (MI) and severe mental disorders (SMDs) are two types of highly prevalent and complex disorders and seem to have a relatively high possibility of mortality. However, the contributions of common and rare genetic variants to their comorbidity arestill unclear. Methods: We conducted a combined genome-wide association study (GWAS) and exome-wide association study (EWAS) approach. Results: Using gene-based and gene-set association analyses based on the results of GWAS, we found the common genetic underpinnings of nine genes (GIGYF2, KCNJ13, PCCB, STAG1, HLA-C, HLA-B, FURIN, FES, and SMG6) and nine pathways significantly shared between MI and SMDs. Through Mendelian randomization analysis, we found that twenty-seven genes were potential causal genes for SMDs and MI. Based on the exome sequencing data of MI and SMDs patients from the UK Biobank, we found that MUC2 was exome-wide significant in the two diseases. The gene-set analyses of the exome-wide association study indicated that pathways related to insulin processing androgen catabolic process and angiotensin receptor binding may be involved in the comorbidity between SMDs and MI. We also found that six candidate genes were reported to interact with known therapeutic drugs based on the drug–gene interaction information in DGIdb. Conclusions: Altogether, this study revealed the overlap of common and rare genetic underpinning between SMDs and MI and may provide useful insights for their mechanism study and therapeutic investigations.
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Jiang et al. (2024) conducted an observational in Myocardial Infarction and Severe Mental Disorders (n=200,000). Genetic variants (common and rare) vs. Individuals without the genetic variants or relevant disorders was evaluated on Shared significant genes and pathways between MI and SMDs. Genome-wide and exome-wide association analyses identified nine shared genes and nine pathways between myocardial infarction and severe mental disorders, with MUC2 achieving exome-wide significance.
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