Identification of PTCSC3 as a novel locus for large-vessel ischemic stroke: A genome-wide association study

Tsong Hai Lee, Tai-Ming Ko, Chien Hsiun Chen, Ming Ta Michael Lee, Yeu Jhy Chang, Chien Hung Chang, Kuo Lun Huang, Ting Yu Chang, Jiann Der Lee, Ku Chou Chang, Jen Tsung Yang, Ming Shien Wen, Chao Yung Wang, Ying Ting Chen*, Chia San Hsieh, Shu Yu Chou, Yi Min Liu, Hui Wen Chen, Hung Ting Liao, Chia Wen WangShih Ping Chen, Liang Suei Lu, Yuan Tsong Chen, Jer Yuarn Wu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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. Methods and 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=3.10910 -8 ), rs934075 (P=4.00910 -9 ), rs944289 (P=3.57910 -8 ), rs2787417 (P=1.76910 -8 ), and rs1952706 (P=2.92910 -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<5910 -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.

Original languageEnglish
Article numbere003003
JournalJournal of the American Heart Association
Volume5
Issue number3
DOIs
StatePublished - 1 Jan 2015

Keywords

  • Atherosclerosis
  • Genome-wide association study
  • Non-coding RNA
  • Polymorphism
  • Stroke

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