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

doi:10.1371/journal.pone.0139262

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

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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 language	English
Article number	e0139262
Journal	PloS one
Volume	10
Issue number	10
DOIs	https://doi.org/10.1371/journal.pone.0139262
Publication status	Published - 21-10-2015
Externally published	Yes

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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, 10(10), Article e0139262. https://doi.org/10.1371/journal.pone.0139262

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title = "Genome-wide association study of peripheral arterial disease in a Japanese population",

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.",

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

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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

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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

N1 - Publisher Copyright: © 2015 Matsukura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2015/10/21

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

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