Many studies have examined the genetic contribution to suicide. However, data on suicide in the Italian population are scarce. We therefore aimed to address this gap by investigating a cohort of 111 Italians for whom a verdict of suicide had been declared in court in Florence, Italy between 2007 and 2017. This cohort included 86 men and 25 women. DNA samples were obtained from tissues or blood, and 22 genes from multiple neurobiological pathways previously shown to be associated with the pathogenesis of suicide were analysed. Next-generation sequencing was used to compare these gene sequences with those from a large, normal population. In this study, we identified 19 gene variants that were present at significantly lower frequencies in our Italian cohort than in the general population. In addition, four missense mutations were identified in four different genes: Monoamine Oxidase A ( MAOA ), 5-Hydroxytryptamine Receptor 2 A ( HTR2A) , Sodium Voltage-Gated Channel Alpha Subunit 8 ( SCN8A ), and Nitric Oxide Synthase 3 ( NOS3 ). Our study identified several potential genetic links with suicide in a cohort of Italians and supports a relationship between specific genetic variants and suicidal behaviour in this population.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): FAS-Salute 2014, regione Toscana Background Sudden cardiac arrest (SCA) or death (SCD) in young people represents a dramatic event, often leading to severe neurologic outcomes or death. However, the incidence of this phenomenon remains largely unknown, since the recording of cases, and consequently the identification of the underlying causes, requires a multi-professional and disciplinary approach, including genetic counselling. Purpose In this study, we aimed to monitor and investigate SCA and SCD in young people (≤50 years) recorded in the ToRSADE© registry comparing clinical and molecular data. Methods and Results A total of 22 blood samples were analyzed; 14 were collected from dead patients during autopsy and 8 from resuscitated patients after cardiac arrest. Next Generation Sequencing (NGS) analysis revealed 38% of total cases with Likely Pathogenetic (LP) variants associated to Cardiomyopathy (CM) or Channelopathy, and 61% with Variant of Uncertain Significance (VUS). In three cases, NGS confirmed autopsy and histology findings: the p.(Leu466Phe) variant in SCN5A associated with Brugada Syndrome (1a), the p.(Glu173del) in TNNT2 for Hypertrophic CM (1b) and the p. (Asn480Lysfs*20) in PKP2 for Arrhythmogenic Cardiomyopathy (AC) (1c). Conclusions Creation of the ToRSADE© registry allowed implementation of a blood repository for molecular and genetic analysis. Genetic analysis combined with clinical information and post-mortem evaluation constitute a multi-disciplinary approach to juvenile SCD and SCA, while providing medical and genetic assistance to families, public awareness especially among youths and athletes, as well as up-to-date research on the underlying mechanisms of cardiomyopathies.