A polygenic risk score to predict sudden cardiac arrest in patients with coronary artery disease

Cardiovascular disease (CVD) is a leading health problem and the main cause of death globally. Even when underlying causative factors are known, it is unclear why a cardiovascular condition causes premature death in a victim while others can live longer with the same condition. Here we propose a combined polygenic risk score (metaPRS) based on coronary artery disease (CAD), myocardial infarction (MI), low-density lipoprotein (LDL) cholesterol, body mass index (BMI) and type 2 diabetes (T2D) to predict the risk of sudden cardiac arrest (SCA) in patients affected by severe cardiovascular conditions. We collected 2,114 patients with reported history of acute coronary syndrome from the Centre Hospitalier Universitaire Vaudois (CHUV) Genomic Biobank (BGC) and extracted data from the UK Biobank (UKB) on 13,696 participants with similar medical history. Among them, 303 and 932 had a further reported diagnosis of SCA or ventricular tachycardia/fibrillation according to the International Classification of Diseases (ICD-10) codes in BGC and UKB, respectively. We demonstrate that the metaPRS is significantly associated with SCA in both cohorts ( OR BGC = 1.28, P BGC = 8.39 × 10−05 and OR UKB = 1.14, P UKB = 7.07 × 10−05). Furthermore, using the diagnosis based on the International Classification of Diseases (ICD-10) codes available in the UKB, the metaPRS exhibits a strong association with the presence of aortocoronary bypass graft ( OR UKB = 1.31, P UKB = 6.93 × 10−33) and coronary angioplasty implant (ORUKB=1.14, PUKB=1.46×10−12). These results show that a combined genetic risk score for CVD and associated risk factors has the potential to predict the occurrence of SCA in patients with myocardial infarction, hence to identify patients who could benefit from further preventive measures. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Migros Pionner Fund, a part of the social commitment of the Migros Group. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Ethical Committee for Human Research of Canton Vaud (Switzerland) approved this study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors