Lab Activities

Laboratory for Cardiovascular Genomics and Informatics

Research Activities

Kaoru Ito portrait

Team Director

Kaoru Ito

Cardiovascular diseases (CVDs) represent the second leading cause of death in Japan and remain the leading cause of mortality worldwide. A comprehensive understanding of their pathogenesis, effective translation of this knowledge into clinical practice, and the identification of novel therapeutic targets are therefore critical global priorities from medical, economic, and societal perspectives. To address these challenges, our research program integrates state-of-the-art approaches—including trans-omics analyses, machine learning, and statistical genetics—to elucidate the genetic architecture of cardiovascular diseases and to accelerate the clinical implementation of genomic information.

Our research encompasses both common and rare cardiovascular conditions. In addition to prevalent disorders such as ischemic heart disease, atrial fibrillation, and heart failure, we focus on rare but clinically significant diseases, including Kawasaki disease, chronic thromboembolic pulmonary hypertension, and cancer therapy–related cardiac dysfunction. Current projects include: (1) large-scale genetic studies of major cardiovascular diseases conducted in collaboration with international consortia, with a particular emphasis on identifying population-specific genetic architectures and differences between Japanese and European cohorts; (2) the development and validation of novel machine learning–based genetic analysis methods designed to overcome the “P > N” challenge, in which the number of genetic variants substantially exceeds the available sample size; and (3) the elucidation of disease mechanisms in rare cardiovascular disorders using multi-omics data derived from multicenter patient cohorts across Japan.

Beyond individual projects, our team contributes substantially to national and international cardiovascular genomics initiatives. Ultimately, our goal is to improve genome-informed diagnosis, risk stratification, and therapeutic strategies for patients with cardiovascular diseases, while supporting clinicians in delivering precision cardiovascular medicine.

Distribution and Genetic Correlation of Heart Failure Subgroups in the Japanese Population

Laboratory for Cardiovascular Genomics and Informatics figure

Distribution and Genetic Correlation of Heart Failure Subgroups in the Japanese Population

Laboratory for Cardiovascular Genomics and Informatics figure

(a) Sample overlap between each HF phenotype in the Japanese. (b) Genetic correlation between HF GWAS. indicates P < 0.05, and * P < 0.0083 (0.05/6). Two-sided uncorrected P values were derived from the LDSC software. (c) Genetic correlation between HF and risk factors. indicates P < 0.05 and * indicates P < 0.00125 (0.05/40 tested pairs). Two-sided uncorrected P values were derived from the LDSC software. AF, atrial fibrillation; BBJ, Biobank Japan; BMI, body mass index; CAD, coronary artery disease; DBP, diastolic blood pressure; DM, diabetes mellitus; EUR, European; GWAS, genome-wide association study; HDL, high-density lipoprotein cholesterol; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LDL, low-density lipoprotein cholesterol; LDSC, linkage disequilibrium score regression; NIHF; non-ischemic heart failure; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride.

(a) Sample overlap between each HF phenotype in the Japanese. (b) Genetic correlation between HF GWAS. indicates P < 0.05, and * P < 0.0083 (0.05/6). Two-sided uncorrected P values were derived from the LDSC software. (c) Genetic correlation between HF and risk factors. indicates P < 0.05 and * indicates P < 0.00125 (0.05/40 tested pairs). Two-sided uncorrected P values were derived from the LDSC software. AF, atrial fibrillation; BBJ, Biobank Japan; BMI, body mass index; CAD, coronary artery disease; DBP, diastolic blood pressure; DM, diabetes mellitus; EUR, European; GWAS, genome-wide association study; HDL, high-density lipoprotein cholesterol; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LDL, low-density lipoprotein cholesterol; LDSC, linkage disequilibrium score regression; NIHF; non-ischemic heart failure; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride.

Recent Major Publications

  1. Enzan N, Miyazawa K, Koyama S, Kurosawa R, Ieki H, Yoshida H, Takechi F, Fukuyama M, Osako R, Tomizuka K, Liu X, Ozaki K, Onouchi Y; BioBank Japan Project; Matsuda K, Momozawa Y, Aburatani H, Kamatani Y, Yamaguchi T, Akazawa H, Node K, Ellinor PT, Levin MG, Damrauer SM, Voight BF, Joseph J, Sun YV, Terao C, Ninomiya T, Komuro I, Ito K. Genome-wide analysis of heart failure yields insights into disease heterogeneity and enables prognostic prediction in the Japanese population. Nat Commun 16, 9680 (2025)

  2. Small AM, Yang TY, Itoh S, Thériault S, Dufresne L, Kurosawa R, Komuro I, Matsuda K, ..., Ito K, Do R, Loos RJF, Schunkert H, Wells QS, Shah SH, Le Tourneau T, Messika-Zeitoun D, Gignoux C, Bundgaard H, Larsson SC, Michaëlsson K, Holm H, Helgadottir A, Esko T, van Heel DA, Mathieu P, Samani NJ, Smith JG, Söderberg S, Rader DJ, Marston NA, Sabatine MS, Pasaniuc B, Cho K, Wilson PWF, O'Donnell CJ, Stefansson K, Bossé Y, Aikawa E, Engert JC, Peloso GM, Natarajan P, Thanassoulis G. Genomic and transcriptomic analyses of aortic stenosis enhance therapeutic target discovery and disease prediction. Nat Genet 58, 57-66 (2025)

  3. Hikino K, Ozaki K, Liu X, Ishikawa Y, Mushiroda T, Terao C. Unraveling time-dependent genetic components underlying alcohol response. Neuropsychopharmacology 50, 1665-1673 (2025)

  4. Roselli C, Surakka I, Olesen MS, Sveinbjornsson G, Marston NA, Choi SH, Holm H, Chaffin M, Gudbjartsson D, Hill MC, Aegisdottir H, Albert CM, Alonso A, Anderson CD, Arking DE, Arnar DO, Barnard J, Benjamin EJ, Braunwald E, Brumpton B, Campbell A, Chami N, Chasman DI, Cho K, Choi EK, Christophersen IE, Chung MK, Conen D, Crijns HJ, Cutler MJ, Czuba T, Damrauer SM, Dichgans M, Dörr M, Dudink E, Duong T, Erikstrup C, Esko T, Fatkin D, Faul JD, Ferreira M, Freitag DF, Ganesh SK, Gaziano JM, Geelhoed B, Ghouse J, Gieger C, Giulianini F, Graham SE, Gudnason V, Guo X, Haggerty C, Hayward C, Heckbert SR, Hveem K, Ito K, ...; BioBank Japan Project; Regeneron Genetics Center; DBDS Genomic Consortium; Ruff CT, Bundgaard H, Willer C, Stefansson K, Ellinor PT. Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases. Nat Genet 57, 539-547 (2025)

  5. Koide R, Nakashima Y, Kojima S, Sotomi Y, Sakata Y, Sakata Y, Ito K, Parrish NF. Pooled screening for endogenous HHV-6 in subjects with coronary artery disease. Virus Genes 61, 239-243 (2025)

Invited Presentations

  • Ito K. "Atrial Fibrillation Genetics: From Discovery to Translation." Advance in basic research in the mechanisms and treatments of atrial fibrillation. The 18th Asia Pacific Heart Rhythm Society (APHRS) Scientific Session, Yokohama, Japan, November 12-15 (2025)

  • Ito K. "Current status of genetic studies in Japan." The 3rd French-Japan SCAD MTG, Osaka, Japan, October 22 (2025)

  • Kurosawa R, Miyazawa K, Koyama S, Ieki H, Yoshida H, Enzan N, Ota F, Fukuyama M, Osako R, Ito K."East Asian-specific genome-wide association study and cross-ancestry meta-analysis reveal the genetic foundations of valvular heart disease and its subtypes". Young Investigator Award Session in Population Science, Genetics and Epidemiology. European Society of Cardiology Congress, Madrid, Spain, August 29-September 1 (2025)

  • Ito K. "Cardiovascular Diseases in Japan: Focus on Women's Health". WOMEN IN SCIENCE, Tokyo, Japan, June 5 (2025)

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