Hirokawa Megumi, Morita Hiroyuki, Tajima Tomoyuki, Takahashi Atsushi, Ashikawa Kyota, Miya Fuyuki, Shigemizu Daichi, Ozaki Kouichi, Sakata Yasuhiko, Nakatani Daisaku, Suna Shinichiro, Imai Yasushi, Tanaka Toshihiro, Tsunoda Tatsuhiko, Matsuda Koichi, Kadowaki Takashi, Nakamura Yusuke, Nagai Ryozo, Komuro Issei, Kubo Michiaki
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.
Department of Translational Research for Healthcare and Clinical Science, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Eur J Hum Genet. 2015 Mar;23(3):374-80. doi: 10.1038/ejhg.2014.110. Epub 2014 Jun 11.
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.
尽管在预防和治疗策略方面取得了显著进展，但心肌梗死（MI）仍是全球主要的死亡原因之一。在欧洲的全基因组关联研究（GWAS）中，总共鉴定出了55个易感基因。然而，来自其他人群的大规模GWAS可能会发现更多的易感基因座。为了尽可能多地鉴定MI易感基因座，我们在日本人群中进行了大规模的基因组分析。为了鉴定日本人中的MI易感基因座，我们使用Illumina Human610-Quad BeadChip和HumanHap550v3基因分型芯片对1666例病例和3198例对照进行了GWAS。我们在日本人群中使用总共11412例病例和28397例对照进行了重复研究。我们的研究确定了两个新的MI易感基因座：位于3p24.3染色体上的PLCL2（rs4618210：A>G，P = 2.60×10^(-9)，优势比（OR）= 0.91）和位于19p13.3染色体上的AP3D1-DOT1L-SF3A2（rs
