Identification of PTCSC3 as a Novel Locus for Large‐Vessel Ischemic Stroke: A Genome‐Wide Association Study

Autor: Tai-Ming Ko, Shih Ping Chen, Liang Suei Lu, Ming Shien Wen, Yi Min Liu, Chao-Yung Wang, Hui Wen Chen, Jer-Yuarn Wu, Ku Chou Chang, Chien-Hsiun Chen, Shu Yu Chou, Ming Ta Michael Lee, Hung Ting Liao, Yuan-Tsong Chen, Tsong Hai Lee, Jiann-Der Lee, Chia San Hsieh, Yeu Jhy Chang, Jen Tsung Yang, Kuo Lun Huang, Ting-Yu Chang, C.W. Wang, Chien Hung Chang, Ying Ting Chen
Rok vydání: 2016
Předmět:
Genetic Markers
Male
0301 basic medicine
Oncology
China
medicine.medical_specialty
Pathology
RNA
Untranslated
Taiwan
Genome-wide association study
Polymorphism
Single Nucleotide
Brain Ischemia
polymorphism
Brain ischemia
Genetic
Association Studies
03 medical and health sciences
0302 clinical medicine
Asian People
Risk Factors
Internal medicine
medicine
Genetic predisposition
Humans
Genetic Predisposition to Disease
Stroke
Aged
Original Research
genome‐wide association study
Ischemic Stroke
Cause of death
business.industry
Case-control study
Middle Aged
medicine.disease
3. Good health
Phenotype
030104 developmental biology
Genetic marker
Case-Control Studies
non‐coding RNA
Female
atherosclerosis
Thyroid function
Cardiology and Cardiovascular Medicine
business
030217 neurology & neurosurgery
Genome-Wide Association Study
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
Popis: 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 PTCSC 3 (encoding papillary thyroid carcinoma susceptibility candidate 3) that were associated with LAA stroke at genome‐wide significance ( P −8 ). Conclusions Our data provide strong support for future studies on the role of PTCSC 3 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.
Databáze: OpenAIRE
Externí odkaz: