Open Access

Identification of EGFLAM, SPATC1L and RNASE13 as novel susceptibility loci for aortic aneurysm in Japanese individuals 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: March 21, 2017     https://doi.org/10.3892/ijmm.2017.2927
  • Pages: 1091-1100
  • Copyright: © Yamada et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

We performed an exome-wide association study (EWAS) to identify genetic variants - in particular, low‑frequency or rare variants with a moderate to large effect size - that confer susceptibility to aortic aneurysm with 8,782 Japanese subjects (456 patients with aortic aneurysm, 8,326 control individuals) and with the use of Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The correlation of allele frequencies for 41,432 single nucleotide polymorphisms (SNPs) that passed quality control to aortic aneurysm was examined with Fisher's exact test. Based on Bonferroni's correction, a P-value of <1.21x10-6 was considered statistically significant. The EWAS revealed 59 SNPs that were significantly associated with aortic aneurysm. None of these SNPs was significantly (P<2.12x10-4) associated with aortic aneurysm by multivariable logistic regression analysis with adjustment for age, gender and hypertension, although 8 SNPs were related (P<0.05) to this condition. Examination of the correlation of these latter 8 SNPs to true or dissecting aortic aneurysm separately showed that rs1465567 [T/C (W229R)] of the EGF-like, fibronectin type III, and laminin G domains gene (EGFLAM) (dominant model; P=0.0014; odds ratio, 1.63) was significantly (P<0.0016) associated with true aortic aneurysm. We next performed EWASs for true or dissecting aortic aneurysm separately and found that 45 and 19 SNPs were significantly associated with these conditions, respectively. Multivariable logistic regression analysis with adjustment for covariates revealed that rs113710653 [C/T (E231K)] of the spermatogenesis- and centriole associated 1-like gene (SPATC1L) (dominant model; P=0.0002; odds ratio, 5.32) and rs143881017 [C/T (R140H)] of the ribonuclease A family member 13 gene (RNASE13) (dominant model; P=0.0006; odds ratio, 5.77) were significantly (P<2.78x10-4 or P<6.58x10-4, respectively) associated with true or dissecting aortic aneurysm, respectively. EGFLAM and SPATC1L may thus be susceptibility loci for true aortic aneurysm and RNASE13 may be such a locus for dissecting aneurysm in Japanese individuals.
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May-2017
Volume 39 Issue 5

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 EGFLAM, SPATC1L and RNASE13 as novel susceptibility loci for aortic aneurysm in Japanese individuals by exome-wide association studies. Int J Mol Med 39: 1091-1100, 2017
APA
Yamada, Y., Sakuma, J., Takeuchi, I., Yasukochi, Y., Kato, K., Oguri, M. ... Tanaka, M. (2017). Identification of EGFLAM, SPATC1L and RNASE13 as novel susceptibility loci for aortic aneurysm in Japanese individuals by exome-wide association studies. International Journal of Molecular Medicine, 39, 1091-1100. https://doi.org/10.3892/ijmm.2017.2927
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 EGFLAM, SPATC1L and RNASE13 as novel susceptibility loci for aortic aneurysm in Japanese individuals by exome-wide association studies". International Journal of Molecular Medicine 39.5 (2017): 1091-1100.
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 EGFLAM, SPATC1L and RNASE13 as novel susceptibility loci for aortic aneurysm in Japanese individuals by exome-wide association studies". International Journal of Molecular Medicine 39, no. 5 (2017): 1091-1100. https://doi.org/10.3892/ijmm.2017.2927