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Exome sequencing study revealed novel susceptibility loci in subarachnoid hemorrhage (SAH).
Molecular Brain ( IF 3.3 ) Pub Date : 2020-05-25 , DOI: 10.1186/s13041-020-00620-6
Xiwa Hao 1 , Jiangxia Pang 1 , Ruiming Li 1 , Lin Lv 1 , Guorong Liu 1 , Yuechun Li 1 , Guojuan Cheng 1 , Jingfen Zhang 1
Affiliation  

To expand our current understanding of the genetic basis of subarachnoid hemorrhage (SAH), and reveal the susceptibility genes in SAH risk. We conducted whole-exome sequencing (WES) in a cohort of 196 individuals, including 94 SAH patients and 94 controls, as well as 8 samples that belong to two pedigrees. Systematically examination for rare variations (through direct genotyping) and common variations (through genotyping and imputation) for SAHs were performed in this study. A total of 16,029 single-nucleotide polymorphisms (SNPs) and 108,999 short indels were detected in all samples, and among them, 30 SNPs distributed on 17 genes presented a strong association signal with SAH. Two novel pathogenic gene variants were identified as associated risk loci, including mutation in TPO and PALD1. The statistical analysis for rare, damaging variations in SAHs identified several susceptibility genes which were involved in degradation of the extracellular matrix and transcription factor signal pathways. And 25 putative pathogenic genes for SAH were also identified basic on functional interaction network analysis with the published SAH-associated genes. Additionally, pedigree analysis revealed autosomal dominant inheritance of pathogenic genes. Systematical analysis revealed a key role for rare variations in SAH risk and discovered SNPs in new complex loci. Our study expanded the list of candidate genes associated with SAH risk, and will facilitate the investigation of disease-related mechanisms and potential clinical therapies.

中文翻译:

外显子组测序研究揭示了蛛网膜下腔出血(SAH)中的新型易感基因座。

扩展我们目前对蛛网膜下腔出血(SAH)的遗传基础的了解,并揭示SAH风险中的易感基因。我们对196名个体进行了全基因组测序(WES),其中包括94名SAH患者和94名对照,以及8个属于两个家谱的样本。在这项研究中,对SAH的罕见变异(通过直接基因分型)和常见变异(通过基因分型和插补)进行了系统检查。在所有样本中共检测到16,029个单核苷酸多态性(SNP)和108,999个短插入缺失,其中分布在17个基因上的30个SNP与SAH呈现强关联信号。两种新的致病基因变异被确定为相关的风险基因座,包括TPO和PALD1中的突变。对罕见的统计分析,SAHs的破坏性变异确定了几个易感基因,这些基因参与细胞外基质和转录因子信号通路的降解。在与已发表的SAH相关基因进行功能相互作用网络分析的基础上,还鉴定出25种推定的SAH致病基因。此外,谱系分析揭示了致病基因的常染色体显性遗传。系统分析揭示了SAH风险罕见变化的关键作用,并在新的复杂基因座中发现了SNP。我们的研究扩大了与SAH风险相关的候选基因的清单,并将有助于疾病相关机制和潜在临床疗法的研究。在与已发表的SAH相关基因进行功能相互作用网络分析的基础上,还鉴定出25种推定的SAH致病基因。此外,谱系分析揭示了致病基因的常染色体显性遗传。系统分析揭示了SAH风险罕见变化的关键作用,并在新的复杂基因座中发现了SNP。我们的研究扩大了与SAH风险相关的候选基因的清单,并将有助于疾病相关机制和潜在临床疗法的研究。在与已发表的SAH相关基因进行功能相互作用网络分析的基础上,还鉴定出25种推定的SAH致病基因。此外,谱系分析揭示了致病基因的常染色体显性遗传。系统分析揭示了SAH风险罕见变化的关键作用,并在新的复杂基因座中发现了SNP。我们的研究扩大了与SAH风险相关的候选基因的清单,并将有助于疾病相关机制和潜在临床疗法的研究。系统分析揭示了SAH风险罕见变化的关键作用,并在新的复杂基因座中发现了SNP。我们的研究扩大了与SAH风险相关的候选基因的清单,并将有助于疾病相关机制和潜在临床疗法的研究。系统分析揭示了SAH风险罕见变化的关键作用,并在新的复杂基因座中发现了SNP。我们的研究扩大了与SAH风险相关的候选基因的清单,并将有助于疾病相关机制和潜在临床疗法的研究。
更新日期:2020-05-25
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