title: A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese.
abstract: Despite considerable progress in preventive and therapeutic strategies, myocardial infarction (MI) is one of the leading causes of death throughout the world. A total of 55 susceptibility genes have been identified mostly in European genome-wide association studies (GWAS). Nevertheless, large-scale GWAS from other population could possibly find additional susceptibility loci. To identify as many MI susceptibility loci as possible, we performed a large-scale genomic analysis in Japanese population. To identify MI susceptibility loci in Japanese, we conducted a GWAS using 1666 cases and 3198 controls using the Illumina Human610-Quad BeadChip and HumanHap550v3 Genotyping BeadChip. We performed replication studies using a total of 11,412 cases and 28,397 controls in the Japanese population. Our study identified two novel susceptibility loci for MI: PLCL2 on chromosome 3p24.3 (rs4618210:A>G, P = 2.60 × 10(-9), odds ratio (OR) = 0.91) and AP3D1-DOT1L-SF3A2 on chromosome 19p13.3 (rs3803915:A>C, P = 3.84 × 10(-9), OR = 0.89). Besides, a total of 14 previously reported MI susceptibility loci were replicated in our study. In particular, we validated a strong association on chromosome 12q24 (rs3782886:A>G: P = 1.14 × 10(-14), OR = 1.46). Following pathway analysis using 265 genes related to MI or coronary artery disease, we found that these loci might be involved in the pathogenesis of MI via the promotion of atherosclerosis. In the present large-scale genomic analysis, we identified PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for MI in the Japanese population. Our findings will add novel findings for MI susceptibility loci.
authors.affiliation: 1] Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN Yokohama Institute, Yokohama, Japan [2] Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Hirokawa
authors.affiliation: Department of Translational Research for Healthcare and Clinical Science, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.affiliation: 1] Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN Yokohama Institute, Yokohama, Japan [2] Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tajima
authors.affiliation: Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN Yokohama Institute, Yokohama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN Yokohama Institute, Yokohama, Japan.
authors.forename: Kyota
authors.initials: K
authors.lastname: Ashikawa
authors.affiliation: Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN Yokohama Institute, Yokohama, Japan.
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Miya
authors.affiliation: Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN Yokohama Institute, Yokohama, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Shigemizu
authors.affiliation: Laboratory for Cardiovascular Diseases, Center for Genomic Medicine, RIKEN Yokohama Institute, Yokohama, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ozaki
authors.affiliation: 1] Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan [2] Department of Advanced Cardiovascular Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan [3] Department of Evidence-based Cardiovascular Medicine and Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sakata
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Nakatani
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Suna
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Imai
authors.affiliation: Laboratory for Cardiovascular Diseases, Center for Genomic Medicine, RIKEN Yokohama Institute, Yokohama, Japan.
authors.forename: Toshihiro
authors.identifier: 0000000162019784
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN Yokohama Institute, Yokohama, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Koichi
authors.identifier: 0000000172922686
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.affiliation: 1] Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan [2] Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.affiliation: Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN Yokohama Institute, Yokohama, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
mesh_terms: D033963:Adaptor Protein Complex 3 / Q000235:genetics*; D033981:Adaptor Protein Complex delta Subunits / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12; D005260:Female; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: C491904:AP3D1 protein, human; D033963:Adaptor Protein Complex 3; D033981:Adaptor Protein Complex delta Subunits; D047908:Intracellular Signaling Peptides and Proteins; C530632:PLCL2 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C083433:SF3A2 protein, human; C473477:DOT1L protein, human; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase