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

Research output: Contribution to journalArticle

23 Citations (Scopus)

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

Fingerprint

Genome-Wide Association Study
Myocardial Infarction
Chromosomes
Odds Ratio
Population
Genes
Coronary Artery Disease
Cause of Death
Atherosclerosis

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

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. / A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese. In: European Journal of Human Genetics. 2015 ; Vol. 23, No. 3. pp. 374-380.
@article{c773484f7688457088a7cbaa89a868a1,
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.",
author = "Megumi Hirokawa and Hiroyuki Morita and Tomoyuki Tajima and Atsushi Takahashi and Kyota Ashikawa and Fuyuki Miya and Daichi Shigemizu and Kouichi Ozaki and Yasuhiko Sakata and Daisaku Nakatani and Shinichiro Suna and Yasushi Imai and Toshihiro Tanaka and Tatsuhiko Tsunoda and Koichi Matsuda and Takashi Kadowaki and Yusuke Nakamura and Ryozo Nagai and Issei Komuro and Michiaki Kubo",
year = "2015",
month = "3",
day = "1",
doi = "10.1038/ejhg.2014.110",
language = "English",
volume = "23",
pages = "374--380",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "Nature Publishing Group",
number = "3",

}

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, vol. 23, no. 3, pp. 374-380. https://doi.org/10.1038/ejhg.2014.110

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

In: European Journal of Human Genetics, Vol. 23, No. 3, 01.03.2015, p. 374-380.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese

AU - Hirokawa, Megumi

AU - Morita, Hiroyuki

AU - Tajima, Tomoyuki

AU - Takahashi, Atsushi

AU - Ashikawa, Kyota

AU - Miya, Fuyuki

AU - Shigemizu, Daichi

AU - Ozaki, Kouichi

AU - Sakata, Yasuhiko

AU - Nakatani, Daisaku

AU - Suna, Shinichiro

AU - Imai, Yasushi

AU - Tanaka, Toshihiro

AU - Tsunoda, Tatsuhiko

AU - Matsuda, Koichi

AU - Kadowaki, Takashi

AU - Nakamura, Yusuke

AU - Nagai, Ryozo

AU - Komuro, Issei

AU - Kubo, Michiaki

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84938422373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938422373&partnerID=8YFLogxK

U2 - 10.1038/ejhg.2014.110

DO - 10.1038/ejhg.2014.110

M3 - Article

VL - 23

SP - 374

EP - 380

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

IS - 3

ER -