Genome-Wide and Exome-Wide Association Study Identifies Genetic Underpinning of Comorbidity between Myocardial Infarction and Severe Mental Disorders

• Published in: Biomedicines Vol. 12; no. 10; p. 2298
• Main Authors: Jiang, Bixuan, Li, Xiangyi, Li, Mo, Zhou, Wei, Zhao, Mingzhe, Wu, Hao, Zhang, Na, Shen, Lu, Wan, Chunling, He, Lin, Huai, Cong, Qin, Shengying
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.10.2024; MDPI
• Subjects: Analysis; Angiotensin; association study; Biobanks; Bipolar disorder; Cardiac patients; China; Comorbidity; Development and progression; Disease; Drug development; Drug interaction; EWAS; Genes; Genetic analysis; Genetic diversity; Genome-wide association studies; Genomes; Genomics; GWAS; Health aspects; Heart attack; Heart attacks; Histocompatibility antigen HLA; Histocompatibility antigens; HLA histocompatibility antigens; Information processing; Loneliness; mental disorder; Mental disorders; Mental illness; Metabolism; Morocco; Mortality; Myocardial infarction; Nervous system; Population; Quality control; Schizophrenia; Whole genome sequencing; Morocco; China; United Kingdom > UK; GWAS; comorbidity; mental disorder; EWAS; association study; myocardial infarction
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines12102298

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. We conducted a combined genome-wide association study (GWAS) and exome-wide association study (EWAS) approach. Using gene-based and gene-set association analyses based on the results of GWAS, we found the common genetic underpinnings of nine genes ( , , , , , , , , and ) 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 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. 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.