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Two Novel Susceptibility SNPs for Ischemic Stroke Using Exome Sequencing in Chinese Han Population

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Abstract

Genome-wide association studies (GWAS) of ischemic stroke (IS) have been performed on several cohorts of Caucasian or African population and Japanese, resulting in somewhat inconsistent conclusion. We aimed to identify susceptibility loci for IS by exome sequencing in a Chinese Han population. Exome sequencing was used to screen susceptibility loci among 100 cases and 100 matched controls. Significant SNPs from the first stage were verified in up to 3,554 participants from three hospital-based case–control studies. In the initial exome sequencing analysis, rs10489177 in c1orf156 gene located on chromosome 1q24 (p < 1 × 10−8) and rs17118 in XYLB gene located on chromosome 3p21 (p < 1 × 10−6) were found to be significantly associated with IS. In the following validation stage, significantly increased odds ratios were observed in individuals with rs10489177 GG (OR = 2.02, 95 % CI = 1.35–3.03) or rs17118 AA genotype (OR = 1.50, 95 % CI = 1.17–1.91). The rs10489177 GG genotype was associated with significantly increased risk for IS in individuals without hypertension (OR = 2.78, 95 % CI = 1.59–4.86) and in individuals without diabetes (OR = 1.93, 95 % CI = 1.27–2.94). In contrast, the rs17118 AA genotype may significantly increase the risk for IS, particularly for individuals with hypertension (OR = 1.73, 95 % CI = 1.08–2.78) and for individuals without diabetes (OR = 1.52, 95 % CI = 1.17–1.98) or non-smoker (OR = 1.59, 95 % CI = 1.16–2.19). Collectively, our study identified two novel loci (rs17118 and rs10489177) which were associated with an increased risk for IS in Chinese Han populations. Further studies are needed to confirm these associations in other populations and elucidate the biological mechanisms underlying the observed associations.

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Abbreviations

GWAS:

genome-wide associated study

IS:

ischemic stroke

SNP:

single nucleotide polymorphism

SD:

standard deviation

XYLB:

xylulokinase homolog gene

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Acknowledgments

We thank Dr. Xiaofan Chu and Dr. Yi Guo for their efforts in recruiting patients and control subjects for this work. We want to especially acknowledge all the participants in this study. This work was supported by grants from the Scientific and Technological Development Project of Shenzhen (no. 201001018) and the China Postdoctoral Scientific Foundation (no. 20110491140), as well as a research fund (no. 81302497) from the National Natural Science Foundation of China.

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Authors and Affiliations

  1. Key Laboratory of Molecular Biology of Shenzhen, Center for Disease Control and Prevention, Shenzhen, 518055, China

    Yanwei Zhang, Yijie Geng, Renli Zhang, Yuebin Ke, Li Zhou & Jinquan Cheng

  2. School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Yanwei Zhang & Tangchun Wu

  3. Hubei Center for Disease Control and Prevention, Wuhan, China

    Yeqing Tong

  4. BGI-Shenzhen, Shenzhen, China

    Yong Zhang, Hao Zhang & Zhixiang Yan

  5. Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Hu Ding & Daowen Wang

  6. Department of Thoracic and Cardiovascular Surgery, Futian Hospital, Guang Dong Medical College, Shenzhen, China

    Jingjun Han

  7. Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA

    Frank B. Hu

Authors
  1. Yanwei Zhang
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  2. Yeqing Tong
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  3. Yong Zhang
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  5. Hao Zhang
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  6. Yijie Geng
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  7. Renli Zhang
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  9. Jingjun Han
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  10. Zhixiang Yan
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  11. Li Zhou
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  12. Tangchun Wu
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  13. Frank B. Hu
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  14. Daowen Wang
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  15. Jinquan Cheng
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Corresponding authors

Correspondence to Daowen Wang or Jinquan Cheng.

Additional information

Yanwei Zhang Yeqing Tong, Yong Zhang, and Hu Ding contributed equally to this work.

Hao Zhang Tangchun Wu, and Frank B. Hu contributed equally to this work.

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Zhang, Y., Tong, Y., Zhang, Y. et al. Two Novel Susceptibility SNPs for Ischemic Stroke Using Exome Sequencing in Chinese Han Population. Mol Neurobiol 49, 852–862 (2014). https://doi.org/10.1007/s12035-013-8561-0

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  • DOI: https://doi.org/10.1007/s12035-013-8561-0

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