A Genome-Wide Analysis of a Sudden Cardiac Death Cohort: Identifying Novel Target Variants in the Era of Molecular Autopsy

Abstract

Sudden cardiac death (SCD) is an unexpected natural death due to cardiac causes, usually happening within one hour of symptom manifestation or in individuals in good health up to 24 h before the event. Genomic screening has been increasingly applied as a useful approach to detecting the genetic variants that potentially contribute to SCD and helping the evaluation of SCD cases in the post-mortem setting. Our aim was to identify the genetic markers associated with SCD, which might enable its target screening and prevention. In this scope, a case–control analysis through the post-mortem genome-wide screening of 30 autopsy cases was performed. We identified a high number of novel genetic variants associated with SCD, of which 25 polymorphisms were consistent with a previous link to cardiovascular diseases. We ascertained that many genes have been already linked to cardiovascular system functioning and diseases and that the metabolisms most implicated in SCD are the lipid, cholesterol, arachidonic acid, and drug metabolisms, suggesting their roles as potential risk factors. Overall, the genetic variants pinpointed herein might be useful markers of SCD, but the novelty of these results requires further investigations.

From flesh to bones: Multi‐omics approaches in forensic science

“…A particular interest was raised by the missense variant rs2228314 in the SREBF2 gene, associated with the metabolism of cholesterol, responsible for the insurgence of coronary atherosclerosis, a known cause of SCD. This hypothesis was also confirmed by the presence of CACNA1C, KCND2 and PRKAG2 variants all associated with lipid, cholesterol, arachidonic acid, and xenobiotics/drugs metabolisms [149]. Interestingly, the same study identified genetic variants mapping involved drug metabolism (i.e., ABCB1, ABCB2, CYP2E1, CYP2C9 and CYP2J2).…”

“…The findings of this study confirmed the presence of several genetic variants that can be associated with SCD. These results contribute to our understanding of the genetic factors underlying SCD and provide valuable insights for forensic pathology and clinical practice [149]. The study, employing Illumina sequencing, identified 25 SNPs that may be indicative of a potential pathogenic association with SCD.…”

“…These findings suggested the combined effects of drug abuse and arachidonic acid metabolism could be related to the incidence of SCD. This underscores the complex inter-play of genetic and environmental factors in contributing to SCD risk [149].…”

New Insights on Molecular Autopsy in Sudden Death: A Systematic Review

“…Table S2: PRISMA 2020 Main Checklist. References [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 57 ] are cited in Supplementary Materials.…”