1. Identification of PTCSC3 as a Novel Locus for Large-Vessel Ischemic Stroke: A Genome-Wide Association Study.
- Author
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Lee TH, Ko TM, Chen CH, Lee MT, Chang YJ, Chang CH, Huang KL, Chang TY, Lee JD, Chang KC, Yang JT, Wen MS, Wang CY, Chen YT, Hsieh CS, Chou SY, Liu YM, Chen HW, Liao HT, Wang CW, Chen SP, Lu LS, Chen YT, and Wu JY
- Subjects
- Aged, Asian People genetics, Brain Ischemia diagnosis, Brain Ischemia ethnology, Case-Control Studies, China ethnology, Female, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Phenotype, Risk Factors, Stroke diagnosis, Stroke ethnology, Taiwan epidemiology, Brain Ischemia genetics, Polymorphism, Single Nucleotide, RNA, Untranslated genetics, Stroke genetics
- 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=3.10×10(-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., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)
- Published
- 2016
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