A meta-analytic and meta-regression study of postmortem genetic analysis in sudden death: A step towards precision...

Sudden unexpected deaths, even with extensive post-mortem analyses, leave many cases distressingly inconclusive. But molecular autopsy using advanced genetic analysis is a promising way to identify underlying causes that may elude traditional techniques. It gives vital answers to the families of the deceased, and also drives novel research paths.

To determine the diagnostic yield of post-mortem genetic analysis in cases of sudden death.

Articles search was carried out using the keywords "sudden death", "deaths", "unexpected death", "genetic autopsy", "post-mortem genetic analysis" and "molecular autopsy" in Pubmed and Embase databases yielded total of 6005 articles. After title, abstract and full text screening, a total of 14 articles were included for the systematic analysis and meta-analysis.

The results of the meta-analysis revealed a 53.2 % higher prevalence of sudden death in males with 95 % confidence interval of 0.379-0.684 (p < 0.001; I²= 95.43 %). Estimation of the diagnostic yield of the post-mortem genetic analysis revealed the pooled prevalence of 22.1 % with 95 % CI of 0.149-0.293 (p < 0.001) indicating the probability of P/LP variants contributing to cause of death was found in 22.1 % of the cases that underwent post-mortem genetic analysis. The studies that had an overall influence on the effect size and contributing to the heterogeneity were identified by sensitivity analysis using a leave-one-out method. While individual study estimates varied, most ranged between 0.20-0.23 showing no significant shift in the overall estimate, indicating robustness. Random effect meta regression analysis showed no significant relationship was found between the samples and methods used for genetic analysis and diagnostic yield of post-mortem genetic analysis.

To the best of our knowledge, the current systematic review and meta-analysis is the first to thoroughly evaluate the diagnostic yield of the post-mortem genetic analysis in sudden death cases. Molecular autopsy presents a potential method for decoding the genetic causes of sudden death; nevertheless, this study's diagnostic yield should be considered a preliminary estimate. This yield could rise as many parts of the world integrate molecular tools into their autopsy practices and also genetic testing advancements become more widely used.