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.
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SC, ZX and YL are joint first authors.
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.
Patient consent for publication Not required.
Ethics approval The study was approved by the ethics committees of Beijing Tiantan Hospital and all other research centres according to the principles expressed in the Declaration of Helsinki.
Provenance and peer review Not commissioned; internally peer reviewed.
Data availability statement Data are available upon reasonable request. Data in this article are available upon reasonable request.
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