Author
Yoshihiro Onouchi
Other affiliations: University of Tokyo, Osaka University
Bio: Yoshihiro Onouchi is an academic researcher from Chiba University. The author has contributed to research in topics: Genome-wide association study & Kawasaki disease. The author has an hindex of 28, co-authored 59 publications receiving 2685 citations. Previous affiliations of Yoshihiro Onouchi include University of Tokyo & Osaka University.
Papers published on a yearly basis
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Tokyo Medical and Dental University1, Boston Children's Hospital2, University of California, San Diego3, Harvard University4, Jichi Medical University5, Saitama Prefectural University6, Shinshu University7, Kawasaki Medical School8, Fukuoka University9, Subaru10, Toho University11, Fujita Health University12, Dokkyo Medical University13, Keio University14, University of Tokyo15
TL;DR: A functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions is identified.
Abstract: Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q132 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis
414 citations
TL;DR: A genome-wide association study of Kawasaki disease in Japanese subjects using data from 428 individuals with Kawasaki Disease and 3,379 controls genotyped at 473,803 SNPs provides new insights into the pathogenesis and pathophysiology of Kaw Osaka disease.
Abstract: We performed a genome-wide association study (GWAS) of Kawasaki disease in Japanese subjects using data from 428 individuals with Kawasaki disease (cases) and 3,379 controls genotyped at 473,803 SNPs. We validated the association results in two independent replication panels totaling 754 cases and 947 controls. We observed significant associations in the FAM167A-BLK region at 8p22-23 (rs2254546, P = 8.2 × 10(-21)), in the human leukocyte antigen (HLA) region at 6p21.3 (rs2857151, P = 4.6 × 10(-11)) and in the CD40 region at 20q13 (rs4813003, P = 4.8 × 10(-8)). We also replicated the association of a functional SNP of FCGR2A (rs1801274, P = 1.6 × 10(-6)) identified in a recently reported GWAS of Kawasaki disease. Our findings provide new insights into the pathogenesis and pathophysiology of Kawasaki disease.
264 citations
TL;DR: A distinct ethnic difference of genetic background of CD is revealed that was reported previously in other genes between Japanese and Caucasian populations and is now recognised as a robust tool for the identification of susceptibility genes for complex diseases.
Abstract: Inflammatory bowel diseases, Crohn’s disease (CD) and ulcerative colitis are characterised by chronic transmural, segmental and typically granulomatous inflammation of the gut. Each has a peak age of onset in the second to fourth decades of life and prevalence has been increasing significantly in both Western countries and Japan over the last decade, while their pathogenesis remains largely unknown. Recently, positive association of CD with the variants in interleukin 23 receptor (IL23R), autophagy-related 16-like 1 (ATG16L1) genes and chromosome 5p13.1 locus was reported through genome-wide association studies which are now recognised as a robust tool for the identification of susceptibility genes for complex diseases. To examine an association of reported susceptible variants in the three loci with Japanese CD patients, a total of 484 CD patients and 439 controls were genotyped. No evidence of positive association for any of these loci with CD was found in the Japanese population, even after clinically stratified subgroups of CD were used. Our result revealed a distinct ethnic difference of genetic background of CD that we reported previously in other genes between Japanese and Caucasian populations. Further genetic studies are required to confirm our findings with ethnically divergent populations.
226 citations
Kyushu University1, University of Tokyo2, Chiba University3, Seoul National University4, Kyoto University5, Kansai Medical University6, Kyoto Prefectural University of Medicine7, Kindai University8, Shiga University of Medical Science9, Saga University10, University of Tokushima11, University of Shizuoka12, Hiroshima University13, Nagoya University14, Osaka University15, Tohoku University16, Kwansei Gakuin University17
TL;DR: A large-scale genome-wide association study of 168,228 individuals of Japanese ancestry with genotype imputation with genotypes imputation detected eight new susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality, and a trans-ancestry meta-analysis found 35 additional new loci.
Abstract: To elucidate the genetics of coronary artery disease (CAD) in the Japanese population, we conducted a large-scale genome-wide association study of 168,228 individuals of Japanese ancestry (25,892 cases and 142,336 controls) with genotype imputation using a newly developed reference panel of Japanese haplotypes including 1,781 CAD cases and 2,636 controls. We detected eight new susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality. We then conducted a trans-ancestry meta-analysis and discovered 35 additional new loci. Using the meta-analysis results, we derived a polygenic risk score (PRS) for CAD, which outperformed those derived from either Japanese or European genome-wide association studies. The PRS prioritized risk factors among various clinical parameters and segregated individuals with increased risk of long-term cardiovascular mortality. Our data improve the clinical characterization of CAD genetics and suggest the utility of trans-ancestry meta-analysis for PRS derivation in non-European populations.
155 citations
University of California, San Diego1, Boston Children's Hospital2, Wakayama Medical University3, Chiba University4, Toho University5, Fujita Health University6, Dokkyo Medical University7, International University of Health and Welfare8, Kawasaki Medical School9, Subaru10, Harvard University11, Northwestern University12, Jichi Medical University13, Shinshu University14, University of Tokyo15
TL;DR: It is reported that multiple variants in the caspase-3 gene (CASP3) that are in linkage disequilibrium confer susceptibility to KD in both Japanese and US subjects of European ancestry.
Abstract: Kawasaki disease (KD; OMIM 611775) is an acute vasculitis syndrome which predominantly affects small- and medium-sized arteries of infants and children. Epidemiological data suggest that host genetics underlie the disease pathogenesis. Here we report that multiple variants in the caspase-3 gene (CASP3) that are in linkage disequilibrium confer susceptibility to KD in both Japanese and US subjects of European ancestry. We found that a G to A substitution of one commonly associated SNP located in the 5′ untranslated region of CASP3 (rs72689236; P = 4.2 × 10−8 in the Japanese and P = 3.7 × 10−3 in the European Americans) abolished binding of nuclear factor of activated T cells to the DNA sequence surrounding the SNP. Our findings suggest that altered CASP3 expression in immune effecter cells influences susceptibility to KD.
135 citations
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TL;DR: Dariush Mozaffarian, Michael E. Mussolino, Graham Nichol, Nina P. Paynter, Wayne D. Sorlie, Randall S. Stafford, Tanya N. Turan, Melanie B. Turner, Nathan D. Turner.
Abstract: Rosamond, Paul D. Sorlie, Randall S. Stafford, Tanya N. Turan, Melanie B. Turner, Nathan D. Dariush Mozaffarian, Michael E. Mussolino, Graham Nichol, Nina P. Paynter, Wayne D. Ariane Marelli, David B. Matchar, Mary M. McDermott, James B. Meigs, Claudia S. Moy, Lackland, Judith H. Lichtman, Lynda D. Lisabeth, Diane M. Makuc, Gregory M. Marcus, John A. Heit, P. Michael Ho, Virginia J. Howard, Brett M. Kissela, Steven J. Kittner, Daniel T. Caroline S. Fox, Heather J. Fullerton, Cathleen Gillespie, Kurt J. Greenlund, Susan M. Hailpern, Todd M. Brown, Mercedes R. Carnethon, Shifan Dai, Giovanni de Simone, Earl S. Ford, Véronique L. Roger, Alan S. Go, Donald M. Lloyd-Jones, Robert J. Adams, Jarett D. Berry, Association 2011 Update : A Report From the American Heart −− Heart Disease and Stroke Statistics
5,311 citations
TL;DR: The American Heart Association's 2020 Impact Goals for Cardiovascular Diseases and Disorders are revealed, with a focus on preventing, treating, and preventing heart disease and stroke.
Abstract: Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e3
1. About These Statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e7
2. American Heart Association's 2020 Impact Goals. . . . . . . . . . . . . . . . .e10
3. Cardiovascular Diseases . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . .e21
4. Subclinical Atherosclerosis . . . . . . . . . . . . . . . . . . . . .e45
5. Coronary Heart Disease, Acute Coronary Syndrome, and Angina Pectoris . . . . . . . . .e54
6. Stroke (Cerebrovascular Disease) . . . . . . . . . . . . . . . . . . . . . . . . . . . .e68
7. High Blood Pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .e88
8. Congenital Cardiovascular Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . .e97
9. Cardiomyopathy and Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . .e102
10. Disorders …
5,260 citations
TL;DR: This year's edition of the Statistical Update includes data on the monitoring and benefits of cardiovascular health in the population, metrics to assess and monitor healthy diets, an enhanced focus on social determinants of health, a focus on the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors, implementation strategies, and implications of the American Heart Association’s 2020 Impact Goals.
Abstract: Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports on the most up-to-date statistics related to heart disease, stroke, and cardiovas...
5,078 citations
TL;DR: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascul...
Abstract: Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascul...
3,034 citations
TL;DR: The introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.
Abstract: The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn's disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.
2,875 citations