A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese

Megumi Hirokawa, Hiroyuki Morita, Tomoyuki Tajima, Atsushi Takahashi, Kyota Ashikawa, Fuyuki Miya, Daichi Shigemizu, Kouichi Ozaki, Yasuhiko Sakata, Daisaku Nakatani, Shinichiro Suna, Yasushi Imai, Toshihiro Tanaka, Tatsuhiko Tsunoda, Koichi Matsuda, Takashi Kadowaki, Yusuke Nakamura, Ryozo Nagai, Issei Komuro, Michiaki Kubo

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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.

Original languageEnglish
Pages (from-to)374-380
Number of pages7
JournalEuropean Journal of Human Genetics
Volume23
Issue number3
DOIs
Publication statusPublished - 01-03-2015

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All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Hirokawa, M., Morita, H., Tajima, T., Takahashi, A., Ashikawa, K., Miya, F., Shigemizu, D., Ozaki, K., Sakata, Y., Nakatani, D., Suna, S., Imai, Y., Tanaka, T., Tsunoda, T., Matsuda, K., Kadowaki, T., Nakamura, Y., Nagai, R., Komuro, I., & Kubo, M. (2015). A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese. European Journal of Human Genetics, 23(3), 374-380. https://doi.org/10.1038/ejhg.2014.110