Genome-wide association study of peripheral arterial disease in a Japanese population

Mitsuru Matsukura, Kouichi Ozaki, Atsushi Takahashi, Yoshihiro Onouchi, Takashi Morizono, Hiroyoshi Komai, Hiroshi Shigematsu, Toshifumi Kudo, Yoshinori Inoue, Hideo Kimura, Akihiro Hosaka, Kunihiro Shigematsu, Teturo Miyata, Toshiaki Watanabe, Tatsuhiko Tsunoda, Michiaki Kubo, Toshihiro Tanaka

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Characteristics of peripheral arterial disease (PAD) are the occlusion or stenosis of multiple vessel sites caused mainly by atherosclerosis and chronic lower limb ischemia. To identify PAD susceptible loci, we conducted a genome-wide association study (GWAS) with 785 cases and 3,383 controls in a Japanese population using 431,666 single nucleotide polymorphisms (SNP). After staged analyses including a total of 3,164 cases and 20,134 controls, we identified 3 novel PAD susceptibility loci at IPO5/RAP2A, EDNRA and HDAC9 with genome wide significance (combined P = 6.8 x 10-14, 5.3 x 10-9 and 8.8 x 10-8, respectively). Fine-mapping at the IPO5/RAP2A locus revealed that rs9584669 conferred risk of PAD. Luciferase assay showed that the risk allele at this locus reduced expression levels of IPO5. To our knowledge, these are the first genetic risk factors for PAD.

Original languageEnglish
Article numbere0139262
JournalPloS one
Volume10
Issue number10
DOIs
Publication statusPublished - 21-10-2015

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Genome-Wide Association Study
Peripheral Arterial Disease
Genes
Association reactions
loci
Population
luciferase
ischemia
atherosclerosis
single nucleotide polymorphism
Disease Susceptibility
disease resistance
Polymorphism
Luciferases
risk factors
Single Nucleotide Polymorphism
Lower Extremity
Assays
alleles
Atherosclerosis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Matsukura, M., Ozaki, K., Takahashi, A., Onouchi, Y., Morizono, T., Komai, H., ... Tanaka, T. (2015). Genome-wide association study of peripheral arterial disease in a Japanese population. PloS one, 10(10), [e0139262]. https://doi.org/10.1371/journal.pone.0139262
Matsukura, Mitsuru ; Ozaki, Kouichi ; Takahashi, Atsushi ; Onouchi, Yoshihiro ; Morizono, Takashi ; Komai, Hiroyoshi ; Shigematsu, Hiroshi ; Kudo, Toshifumi ; Inoue, Yoshinori ; Kimura, Hideo ; Hosaka, Akihiro ; Shigematsu, Kunihiro ; Miyata, Teturo ; Watanabe, Toshiaki ; Tsunoda, Tatsuhiko ; Kubo, Michiaki ; Tanaka, Toshihiro. / Genome-wide association study of peripheral arterial disease in a Japanese population. In: PloS one. 2015 ; Vol. 10, No. 10.
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Matsukura, M, Ozaki, K, Takahashi, A, Onouchi, Y, Morizono, T, Komai, H, Shigematsu, H, Kudo, T, Inoue, Y, Kimura, H, Hosaka, A, Shigematsu, K, Miyata, T, Watanabe, T, Tsunoda, T, Kubo, M & Tanaka, T 2015, 'Genome-wide association study of peripheral arterial disease in a Japanese population', PloS one, vol. 10, no. 10, e0139262. https://doi.org/10.1371/journal.pone.0139262

Genome-wide association study of peripheral arterial disease in a Japanese population. / Matsukura, Mitsuru; Ozaki, Kouichi; Takahashi, Atsushi; Onouchi, Yoshihiro; Morizono, Takashi; Komai, Hiroyoshi; Shigematsu, Hiroshi; Kudo, Toshifumi; Inoue, Yoshinori; Kimura, Hideo; Hosaka, Akihiro; Shigematsu, Kunihiro; Miyata, Teturo; Watanabe, Toshiaki; Tsunoda, Tatsuhiko; Kubo, Michiaki; Tanaka, Toshihiro.

In: PloS one, Vol. 10, No. 10, e0139262, 21.10.2015.

Research output: Contribution to journalArticle

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T1 - Genome-wide association study of peripheral arterial disease in a Japanese population

AU - Matsukura, Mitsuru

AU - Ozaki, Kouichi

AU - Takahashi, Atsushi

AU - Onouchi, Yoshihiro

AU - Morizono, Takashi

AU - Komai, Hiroyoshi

AU - Shigematsu, Hiroshi

AU - Kudo, Toshifumi

AU - Inoue, Yoshinori

AU - Kimura, Hideo

AU - Hosaka, Akihiro

AU - Shigematsu, Kunihiro

AU - Miyata, Teturo

AU - Watanabe, Toshiaki

AU - Tsunoda, Tatsuhiko

AU - Kubo, Michiaki

AU - Tanaka, Toshihiro

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Y1 - 2015/10/21

N2 - Characteristics of peripheral arterial disease (PAD) are the occlusion or stenosis of multiple vessel sites caused mainly by atherosclerosis and chronic lower limb ischemia. To identify PAD susceptible loci, we conducted a genome-wide association study (GWAS) with 785 cases and 3,383 controls in a Japanese population using 431,666 single nucleotide polymorphisms (SNP). After staged analyses including a total of 3,164 cases and 20,134 controls, we identified 3 novel PAD susceptibility loci at IPO5/RAP2A, EDNRA and HDAC9 with genome wide significance (combined P = 6.8 x 10-14, 5.3 x 10-9 and 8.8 x 10-8, respectively). Fine-mapping at the IPO5/RAP2A locus revealed that rs9584669 conferred risk of PAD. Luciferase assay showed that the risk allele at this locus reduced expression levels of IPO5. To our knowledge, these are the first genetic risk factors for PAD.

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Matsukura M, Ozaki K, Takahashi A, Onouchi Y, Morizono T, Komai H et al. Genome-wide association study of peripheral arterial disease in a Japanese population. PloS one. 2015 Oct 21;10(10). e0139262. https://doi.org/10.1371/journal.pone.0139262