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Whole genome sequencing of 10K patients with acute ischaemic stroke or transient ischaemic attack: design, methods and baseline patient characteristics
  1. Si Cheng1,2,3,
  2. Zhe Xu1,2,3,
  3. Yang Liu1,2,3,
  4. Jinxi Lin1,2,
  5. Yong Jiang1,2,
  6. Yilong Wang1,2,
  7. Xia Meng1,2,
  8. Anxin Wang1,2,
  9. Xinying Huang1,2,
  10. Zhimin Wang4,
  11. Guohua Chen5,
  12. Songdi Wu6,
  13. Zhengchang Jia7,
  14. Yongming Chen8,
  15. Xuerong Qiu9,
  16. Jun Wu10,
  17. Binbin Song11,
  18. Weizhong Ji12,
  19. Zhongping An13,
  20. Wenjun Xue14,
  21. Lili Zhao15,
  22. Yu Geng16,
  23. Hongyan Li17,
  24. Hao Li1,2,
  25. Yongjun Wang1,2,3
  1. 1 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  2. 2 China National Clinical Research Center for Neurological Diseases, Beijing, China
  3. 3 Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
  4. 4 Department of Neurology, The First people's Hospital of Taizhou, Taizhou, China
  5. 5 Department of Neurology, Wuhan First Hospital, Wuhan, China
  6. 6 Department of Neurology, The First People's Hospital of Xi'an, Xi'an, China
  7. 7 Department of Neurology, The Second People’s Hospital of Jinzhong, Jinzhong, China
  8. 8 Department of Neurology, WuYuan County People’s Hospital, Bayannur, China
  9. 9 Department of Neurology, Qiqihar City Rongjian Stroke Prevention and Treatment Institute, Qiqihar, China
  10. 10 Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China
  11. 11 Department of Neurology, Luoyang Central Hospital, Luoyang, China
  12. 12 Department of Neurology, Qinghai Provincial People's Hospital, Xining, China
  13. 13 Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China
  14. 14 Department of Neurology, Pingdingshan First People's Hospital, Pingdingshan, China
  15. 15 Department of Neurology, Changzhi People's Hospital, Changzhi, China
  16. 16 Department of Neurology, Zhejiang Provincial People's Hospital, Hangzhou, China
  17. 17 Department of Neurology, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, China
  1. Correspondence to Dr Yongjun Wang; yongjunwang{at}


Background and purpose Stroke is the second leading cause of death worldwide and the leading cause of mortality and long-term disability in China, but its underlying risk genes and pathways are far from being comprehensively understood. We here describe the design and methods of whole genome sequencing (WGS) for 10 914 patients with acute ischaemic stroke or transient ischaemic attack from the Third China National Stroke Registry (CNSR-III).

Methods Baseline clinical characteristics of the included patients in this study were reported. DNA was extracted from white blood cells of participants. Libraries are constructed using qualified DNA, and WGS is conducted on BGISEQ-500 platform. The average depth is intended to be greater than 30× for each subject. Afterwards, Sentieon software is applied to process the sequencing data under the Genome Analysis Toolkit best practice guidance to call genotypes of single nucleotide variants (SNVs) and insertion-deletions. For each included subject, 21 fingerprint SNVs are genotyped by MassARRAY assays to verify that DNA sample and sequencing data originate from the same individual. The copy number variations and structural variations are also called for each patient. All of the genetic variants are annotated and predicted by bioinformatics software or by reviewing public databases.

Results The average age of the included 10 914 patients was 62.2±11.3 years, and 31.4% patients were women. Most of the baseline clinical characteristics of the 10 914 and the excluded patients were balanced.

Conclusions The WGS data together with abundant clinical and imaging data of CNSR-III could provide opportunity to elucidate the molecular mechanisms and discover novel therapeutic targets for stroke.

  • stroke
  • genetic

Data availability statement

Data are available upon reasonable request. Data in this article are available upon reasonable request.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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Data availability statement

Data are available upon reasonable request. Data in this article are available upon reasonable request.

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  • SC, ZX and YL are joint first authors.

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  • Contributors Study concept and design: SC, HaL and YoW. Drafting of the manuscript: SC, ZX and YL. Statistical analysis: AW, XH and ZX. Study supervision and organisation of the project: JL, YJ, XM, HaL, YiW and YoW. Supplying patients: ZW, GC, SW, ZJ, YC, XQ, JW, BS, WJ, ZA, WX, LZ, YG and HoL.

  • Funding This study was supported by grants from the Ministry of Science and Technology of the People’s Republic of China (2016YFC0901002, 2016YFC0901001), Beijing Municipal Science & Technology Commission (D171100003017002),Beijing Municipal Administration of Hospitals’ Mission Plan (SML20150502) and National Science and Technology Major Project (2017ZX09304018). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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