Two Novel Susceptibility SNPs for Ischemic Stroke Using Exome Sequencing in Chinese Han Population

Abstract

Genome-wide association studies (GWAS) of ischemic stroke (IS) have been performed on several cohorts of Caucasian or African population and Japanese, resulting in somewhat inconsistent conclusion. We aimed to identify susceptibility loci for IS by exome sequencing in a Chinese Han population. Exome sequencing was used to screen susceptibility loci among 100 cases and 100 matched controls. Significant SNPs from the first stage were verified in up to 3,554 participants from three hospital-based case-control studies. In the initial exome sequencing analysis, rs10489177 in c1orf156 gene located on chromosome 1q24 (p < 1 × 10(-8)) and rs17118 in XYLB gene located on chromosome 3p21 (p < 1 × 10(-6)) were found to be significantly associated with IS. In the following validation stage, significantly increased odds ratios were observed in individuals with rs10489177 GG (OR = 2.02, 95 % CI = 1.35-3.03) or rs17118 AA genotype (OR = 1.50, 95 % CI = 1.17-1.91). The rs10489177 GG genotype was associated with significantly increased risk for IS in individuals without hypertension (OR = 2.78, 95 % CI = 1.59-4.86) and in individuals without diabetes (OR = 1.93, 95 % CI = 1.27-2.94). In contrast, the rs17118 AA genotype may significantly increase the risk for IS, particularly for individuals with hypertension (OR = 1.73, 95 % CI = 1.08-2.78) and for individuals without diabetes (OR = 1.52, 95 % CI = 1.17-1.98) or non-smoker (OR = 1.59, 95 % CI = 1.16-2.19). Collectively, our study identified two novel loci (rs17118 and rs10489177) which were associated with an increased risk for IS in Chinese Han populations. Further studies are needed to confirm these associations in other populations and elucidate the biological mechanisms underlying the observed associations.

miR‐129‐2‐3p directly targets SYK gene and associates with the risk of ischaemic stroke in a Chinese population

“…The motive that initiates the conduction of this study was the association that we found between SYK gene polymorphism and the risk of IS, which was identified by exome sequencing in one of our previous studies, while not yet published. In recent years, studies about the role of SYK gene in stroke have attracted great research interest.…”

“…The patients were recruited from Shenzhen People's Hospital between June 2014 and December 2016. All cases were inpatients diagnosed with IS for the first time and were recruited based on the appearance of a new and abrupt focal neurological deficit, with neurological symptoms and signs persisting for more than 24 hours, as described previously . IS was confirmed by positive findings on head CT or MRI according to the International Classification of Disease (9th Revision, codes 430 to 438).…”

“…We have previously identified several susceptibility loci for IS in a Chinese Han population . Exome sequencing was used to screen susceptibility loci among 100 cases and 100 matched controls.…”

Next Generation Sequencing for Systematic Assessment of Genetics of Small-Vessel Disease and Lacunar Stroke

“…17,31,32 This approach has been previously reported in other two studies on stroke patients. 33,34 The first one by Zhang et al 2014 applied the exome sequencing analysis to a population of 100 Chinese stroke patients and controls, reporting an association with 2 genes with uncertain significance. Moreover, as reported by the same author, this study is biased by the poor population characterization and by the possible founder effect because of the recruitment area (Beijing and Shenzhen).…”

Advancing stroke genomic research in the age of Trans-Omics big data science: Emerging priorities and opportunities

“…We excluded Matsushita et al (2010) 7 and Zhang et al (2012) 8 which were large candidate gene studies, Zhang et al (2014) 9 which was a whole exome sequencing (WES) study, Cole et al (2012) 10 and Zhou et al ( 2014) 11 which were small WES studies examining 10 and 9 subjects respectively; Opherk et al (2014) 12 which described white mater hyperintensity (WMH) volume in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); Keene et al (2014) 13 which described SNPs significantly associated with Vitamins B6 and B12 in stroke patients (not as a risk of stroke); and Traylor et al (2017) 14 which was not a GWAS study, but an heritability study which also applied genetic risk score.…”