Exome sequencing study revealed novel susceptibility loci in subarachnoid hemorrhage (SAH)
Abstract Aim To expand our current understanding of the genetic basis of subarachnoid hemorrhage (SAH), and reveal the susceptibility genes in SAH risk. Methods We conducted whole-exome sequencing (WES) in a cohort of 196 individuals, including 94 SAH patients and 94 controls, as well as 8 samples t...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-05-01
|
| Series: | Molecular Brain |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13041-020-00620-6 |
| _version_ | 1818188434902089728 |
|---|---|
| author | Xiwa Hao Jiangxia Pang Ruiming Li Lin Lv Guorong Liu Yuechun Li Guojuan Cheng Jingfen Zhang |
| author_facet | Xiwa Hao Jiangxia Pang Ruiming Li Lin Lv Guorong Liu Yuechun Li Guojuan Cheng Jingfen Zhang |
| author_sort | Xiwa Hao |
| collection | DOAJ |
| description | Abstract Aim To expand our current understanding of the genetic basis of subarachnoid hemorrhage (SAH), and reveal the susceptibility genes in SAH risk. Methods 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. Results 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. Conclusion 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. |
| first_indexed | 2024-12-11T23:26:52Z |
| format | Article |
| id | doaj.art-61b1442938b74366ba1b665bd6237c9c |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-11T23:26:52Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-61b1442938b74366ba1b665bd6237c9c2022-12-22T00:46:09ZengBMCMolecular Brain1756-66062020-05-0113111210.1186/s13041-020-00620-6Exome sequencing study revealed novel susceptibility loci in subarachnoid hemorrhage (SAH)Xiwa Hao0Jiangxia Pang1Ruiming Li2Lin Lv3Guorong Liu4Yuechun Li5Guojuan Cheng6Jingfen Zhang7Department of Neurology, Baotou Central HospitalDepartment of Neurology, Baotou Central HospitalDepartment of Neurology, Baotou Central HospitalDepartment of Neurology, Baotou Central HospitalDepartment of Neurology, Baotou Central HospitalDepartment of Neurology, Baotou Central HospitalDepartment of Neurology, Baotou Central HospitalDepartment of Neurology, Baotou Central HospitalAbstract Aim To expand our current understanding of the genetic basis of subarachnoid hemorrhage (SAH), and reveal the susceptibility genes in SAH risk. Methods 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. Results 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. Conclusion 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.http://link.springer.com/article/10.1186/s13041-020-00620-6Subarachnoid hemorrhage (SAH)Whole-exome sequencing (WES)Genome-wide association analysis (GWAS)Rare variationsPedigree analysis |
| spellingShingle | Xiwa Hao Jiangxia Pang Ruiming Li Lin Lv Guorong Liu Yuechun Li Guojuan Cheng Jingfen Zhang Exome sequencing study revealed novel susceptibility loci in subarachnoid hemorrhage (SAH) Molecular Brain Subarachnoid hemorrhage (SAH) Whole-exome sequencing (WES) Genome-wide association analysis (GWAS) Rare variations Pedigree analysis |
| title | Exome sequencing study revealed novel susceptibility loci in subarachnoid hemorrhage (SAH) |
| title_full | Exome sequencing study revealed novel susceptibility loci in subarachnoid hemorrhage (SAH) |
| title_fullStr | Exome sequencing study revealed novel susceptibility loci in subarachnoid hemorrhage (SAH) |
| title_full_unstemmed | Exome sequencing study revealed novel susceptibility loci in subarachnoid hemorrhage (SAH) |
| title_short | Exome sequencing study revealed novel susceptibility loci in subarachnoid hemorrhage (SAH) |
| title_sort | exome sequencing study revealed novel susceptibility loci in subarachnoid hemorrhage sah |
| topic | Subarachnoid hemorrhage (SAH) Whole-exome sequencing (WES) Genome-wide association analysis (GWAS) Rare variations Pedigree analysis |
| url | http://link.springer.com/article/10.1186/s13041-020-00620-6 |
| work_keys_str_mv | AT xiwahao exomesequencingstudyrevealednovelsusceptibilitylociinsubarachnoidhemorrhagesah AT jiangxiapang exomesequencingstudyrevealednovelsusceptibilitylociinsubarachnoidhemorrhagesah AT ruimingli exomesequencingstudyrevealednovelsusceptibilitylociinsubarachnoidhemorrhagesah AT linlv exomesequencingstudyrevealednovelsusceptibilitylociinsubarachnoidhemorrhagesah AT guorongliu exomesequencingstudyrevealednovelsusceptibilitylociinsubarachnoidhemorrhagesah AT yuechunli exomesequencingstudyrevealednovelsusceptibilitylociinsubarachnoidhemorrhagesah AT guojuancheng exomesequencingstudyrevealednovelsusceptibilitylociinsubarachnoidhemorrhagesah AT jingfenzhang exomesequencingstudyrevealednovelsusceptibilitylociinsubarachnoidhemorrhagesah |