title: Identification of PTCSC3 as a Novel Locus for Large-Vessel Ischemic Stroke: A Genome-Wide Association Study.
abstract: BACKGROUND
  Ischemic stroke is a major cause of death and disability in the world. A major ischemic stroke subtype, large-vessel ischemic stroke (large artery atherosclerosis; LAA), has been shown to have some genetic components in individuals of European ancestry. However, it is not clear whether the genetic predisposition to LAA stroke varies among ethnicities. We sought to identify genetic factors that contribute to LAA stroke in 2 independent samples of Han Chinese individuals.
  
  
  RESULTS
  Novel genetic variants that predispose individuals to LAA stroke were identified using a genome-wide association study (GWAS) of 444 individuals with LAA stroke and 1727 controls in a Han Chinese population residing in Taiwan. The study was replicated in an independent Han Chinese population comprising an additional 319 cases and 1802 controls. We identified 5 single-nucleotide polymorphisms, including rs2415317 (P=3.10×10(-8)), rs934075 (P=4.00×10(-9)), rs944289 (P=3.57×10(-8)), rs2787417 (P=1.76×10(-8)), and rs1952706 (P=2.92×10(-8)), at one novel locus on chromosome 14q13.3 within PTCSC3 (encoding papillary thyroid carcinoma susceptibility candidate 3) that were associated with LAA stroke at genome-wide significance (P<5×10(-8)).
  
  
  CONCLUSIONS
  Our data provide strong support for future studies on the role of PTCSC3 in the pathogenesis of LAA stroke and the association between LAA stroke development and thyroid function. In addition, these findings provide insights into the genetic basis of LAA stroke and identify a novel pathway that might be applicable for future therapeutic intervention.
authors.affiliation: Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Tsong-Hai
authors.initials: TH
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Tai-Ming
authors.initials: TM
authors.lastname: Ko
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chien-Hsiun
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan Laboratory for International Alliance on Genomic Research, Core for Genomic Medicine, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
authors.forename: Ming-Ta Michael
authors.initials: MT
authors.lastname: Lee
authors.affiliation: Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Yeu-Jhy
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Kuo-Lun
authors.initials: KL
authors.lastname: Huang
authors.affiliation: Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Chang Gung Memorial Hospital, Chiayi Branch, Chang Gung University College of Medicine, Chiayi, Taiwan.
authors.forename: Jiann-Der
authors.initials: JD
authors.lastname: Lee
authors.affiliation: Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ku-Chou
authors.initials: KC
authors.lastname: Chang
authors.affiliation: Chang Gung Memorial Hospital, Chiayi Branch, Chang Gung University College of Medicine, Chiayi, Taiwan.
authors.forename: Jen-Tsung
authors.initials: JT
authors.lastname: Yang
authors.affiliation: Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Ming-Shien
authors.initials: MS
authors.lastname: Wen
authors.affiliation: Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Chao-Yung
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Ying-Ting
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-San
authors.initials: CS
authors.lastname: Hsieh
authors.affiliation: Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Chou
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Liu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Hung-Ting
authors.initials: HT
authors.lastname: Liao
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Liang-Suei
authors.initials: LS
authors.lastname: Lu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan Department of Pediatrics, Duke University Medical Center, Durham, NC chen0010@ibms.sinica.edu.tw jywu@ibms.sinica.edu.tw.
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan School of Chinese Medicine, China Medical University, Taichung, Taiwan chen0010@ibms.sinica.edu.tw jywu@ibms.sinica.edu.tw.
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D002545:Brain Ischemia / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D022661:RNA, Untranslated / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology
chemical_list: D005819:Genetic Markers; C000603517:Ptcsc3 untranslated RNA, human; D022661:RNA, Untranslated
keywords: atherosclerosis; genome‐wide association study; non‐coding RNA; polymorphism; stroke