{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:28:27Z","timestamp":1787077707616,"version":"build-2736575974"},"reference-count":111,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>The advent of high-throughput sequencing technologies has revolutionized cardiovascular genetics, generating vast amounts of data. A major challenge in the genomic era is the efficient and accurate identification of causative genetic variants associated with cardiovascular disease. Artificial intelligence (AI)-driven computational approaches offer a powerful solution by enabling the automation of variant classification, improving consistency and reproducibility, and enhancing predictive accuracy. These methods may guide not only variant classification, variant effect prediction, and clinical prioritization, but also open the door to data-driven precision medicine, enabling more accurate and individualized diagnoses and targeted therapeutic strategies tailored to each patient\u2019s unique genetic and clinical profile. This state-of-the-art review provides a structured overview of AI methodologies applied to cardiovascular genomics, beginning with rule-based expert systems that encode standardized guidelines for consistent variant interpretation. Next, we examine machine learning approaches capable of identifying complex patterns in annotated multimodal clinical and multi-omic datasets. The role of deep learning algorithms is highlighted for their ability to extract features from high-dimensional, unstructured data relevant to cardiovascular disease. In addition, the potential of generative AI is explored, including applications in synthetic data generation, variant impact prediction, and automated summarization of biomedical literature. Despite advances, several challenges remain, including data heterogeneity, the need for explainable AI models to elucidate the decision mechanisms, and the complexity linked to the integration of AI-based tools into clinical workflows. Addressing these issues requires interdisciplinary collaboration among clinicians, geneticists, data scientists, and bioinformaticians to ensure the effective translation of AI-generated insights into clinical practice. This review aims to provide a comprehensive perspective on the evolving role of AI in cardiovascular genomics and its implications for advancing precision medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.125.005447","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:00:37Z","timestamp":1787076037000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Artificial Intelligence and Machine Learning Approaches for Cardiovascular Genomics: A State-of-the-Art Review"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8027-5666","authenticated-orcid":true,"given":"Federica","family":"De Paoli","sequence":"first","affiliation":[{"name":"enGenome, Pavia, Italy (F.D.P., I.L., S.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7007-0862","authenticated-orcid":true,"given":"Giovanna","family":"Nicora","sequence":"additional","affiliation":[{"name":"Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Italy (G.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9207-8985","authenticated-orcid":true,"given":"Kristian","family":"Galanti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences, \u201cG. D\u2019Annunzio\u201d University of Chieti-Pescara, Italy (K.G., F.R.)."},{"name":"Department of Cardiology, Policlinico Casilino, Rome, Italy (K.G.)"},{"name":"Center for Inherited CV Diseases (Y.I.K., M.A.K., C.A.A.C., K.G.), WellSpan Health, York, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3576-471X","authenticated-orcid":true,"given":"Corinthia S.","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Medical College, Rush University, Chicago, IL (C.S.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3215-1028","authenticated-orcid":true,"given":"Francesca","family":"Mangili","sequence":"additional","affiliation":[{"name":"IDSIA \u2013 Istituto Dalle Molle di Studi sull\u2019Intelligenza Artificiale, USI-SUPSI, Lugano, Switzerland (F.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Smedley","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Queen Mary University of London, United Kingdom (D.S., C.A.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja","family":"Appuswamy","sequence":"additional","affiliation":[{"name":"Data Science Department, EURECOM, Biot, France (R.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8638-6738","authenticated-orcid":true,"given":"Yuka","family":"Imamura Kawasawa","sequence":"additional","affiliation":[{"name":"Department of Cardiology (Y.I.K., M.A.K.), WellSpan Health, York, PA."},{"name":"Center for Inherited CV Diseases (Y.I.K., M.A.K., C.A.A.C., K.G.), WellSpan Health, York, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4045-4341","authenticated-orcid":true,"given":"Virend K.","family":"Somers","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic Rochester, MN (V.K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Limongelli","sequence":"additional","affiliation":[{"name":"enGenome, Pavia, Italy (F.D.P., I.L., S.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5833-8915","authenticated-orcid":true,"given":"Mohamad","family":"AlKhayat","sequence":"additional","affiliation":[{"name":"Department of Cardiology (Y.I.K., M.A.K.), WellSpan Health, York, PA."},{"name":"Center for Inherited CV Diseases (Y.I.K., M.A.K., C.A.A.C., K.G.), WellSpan Health, York, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2352-7230","authenticated-orcid":true,"given":"Bing","family":"Si","sequence":"additional","affiliation":[{"name":"Industrial Engineering, School of Computing and Augmented Intelligence, Arizona State University, Tempe (B.S., C.A.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1401-6623","authenticated-orcid":true,"given":"Fabrizio","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences, \u201cG. 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