Open Access

Identification of six polymorphisms as novel susceptibility loci for ischemic or hemorrhagic stroke by exome-wide association studies

  • Authors:
    • Yoshiji Yamada
    • Jun Sakuma
    • Ichiro Takeuchi
    • Yoshiki Yasukochi
    • Kimihiko Kato
    • Mitsutoshi Oguri
    • Tetsuo Fujimaki
    • Hideki Horibe
    • Masaaki Muramatsu
    • Motoji Sawabe
    • Yoshinori Fujiwara
    • Yu Taniguchi
    • Shuichi Obuchi
    • Hisashi Kawai
    • Shoji Shinkai
    • Seijiro Mori
    • Tomio Arai
    • Masashi Tanaka
  • View Affiliations

  • Published online on: May 3, 2017     https://doi.org/10.3892/ijmm.2017.2972
  • Pages: 1477-1491
  • Copyright: © Yamada et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In this study, we performed exome-wide association studies (EWASs) to identify genetic variants that confer susceptibility to ischemic stroke, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). EWAS for ischemic stroke was performed using 1,575 patients with this condition and 9,210 controls, and EWASs for ICH and SAH were performed using 673 patients with ICH, 265 patients with SAH and 9,158 controls. Analyses were performed with Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The relation of allele frequencies for 41,339 or 41,332 single nucleotide polymorphisms (SNPs) that passed quality control to ischemic or hemorrhagic stroke, respectively, was examined with Fisher's exact test. Based on Bonferroni's correction, a P-value of <1.21x10-6 was considered statistically significant. EWAS for ischemic stroke revealed that 77 SNPs were significantly associated with this condition. Multivariable logistic regression analysis with adjustment for age, sex and the prevalence of hypertension and diabetes mellitus revealed that 4 of these SNPs [rs3212335 of GABRB3 (P=0.0036; odds ratio, 1.29), rs147783135 of TMPRSS7 (P=0.0024; odds ratio, 0.37), rs2292661 of PDIA5 (P=0.0054; odds ratio, 0.35) and rs191885206 of CYP4F12 (P=0.0082; odds ratio, 2.60)] were related (P<0.01) to ischemic stroke. EWASs for ICH or SAH revealed that 48 and 12 SNPs, respectively, were significantly associated with these conditions. Multivariable logistic regression analysis with adjustment for age, sex and the prevalence of hypertension revealed that rs138533962 of STYK1 (P<1.0x10-23; odds ratio, 111.3) was significantly (P<2.60x10-4) associated with ICH and that rs117564807 of COL17A1 (P=0.0009; odds ratio, 2.23x10-8) was significantly (P<0.0010) associated with SAH. GABRB3, TMPRSS7, PDIA5 and CYP4F12 may thus be novel susceptibility loci for ischemic stroke, whereas STYK1 and COL17A1 may be such loci for ICH and SAH, respectively.
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June-2017
Volume 39 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yamada Y, Sakuma J, Takeuchi I, Yasukochi Y, Kato K, Oguri M, Fujimaki T, Horibe H, Muramatsu M, Sawabe M, Sawabe M, et al: Identification of six polymorphisms as novel susceptibility loci for ischemic or hemorrhagic stroke by exome-wide association studies. Int J Mol Med 39: 1477-1491, 2017
APA
Yamada, Y., Sakuma, J., Takeuchi, I., Yasukochi, Y., Kato, K., Oguri, M. ... Tanaka, M. (2017). Identification of six polymorphisms as novel susceptibility loci for ischemic or hemorrhagic stroke by exome-wide association studies. International Journal of Molecular Medicine, 39, 1477-1491. https://doi.org/10.3892/ijmm.2017.2972
MLA
Yamada, Y., Sakuma, J., Takeuchi, I., Yasukochi, Y., Kato, K., Oguri, M., Fujimaki, T., Horibe, H., Muramatsu, M., Sawabe, M., Fujiwara, Y., Taniguchi, Y., Obuchi, S., Kawai, H., Shinkai, S., Mori, S., Arai, T., Tanaka, M."Identification of six polymorphisms as novel susceptibility loci for ischemic or hemorrhagic stroke by exome-wide association studies". International Journal of Molecular Medicine 39.6 (2017): 1477-1491.
Chicago
Yamada, Y., Sakuma, J., Takeuchi, I., Yasukochi, Y., Kato, K., Oguri, M., Fujimaki, T., Horibe, H., Muramatsu, M., Sawabe, M., Fujiwara, Y., Taniguchi, Y., Obuchi, S., Kawai, H., Shinkai, S., Mori, S., Arai, T., Tanaka, M."Identification of six polymorphisms as novel susceptibility loci for ischemic or hemorrhagic stroke by exome-wide association studies". International Journal of Molecular Medicine 39, no. 6 (2017): 1477-1491. https://doi.org/10.3892/ijmm.2017.2972