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Novel genetic susceptibility loci identified by family based whole exome sequencing in Han Chinese schizophrenia patients
Schizophrenia (SCZ) is a highly heritable psychiatric disorder that affects approximately 1% of population around the world. However, early relevant studies did not reach clear conclusions of the genetic mechanisms of SCZ, suggesting that additional susceptibility loci that exert significant influen...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026419/ https://www.ncbi.nlm.nih.gov/pubmed/32066673 http://dx.doi.org/10.1038/s41398-020-0708-y |
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author | Li, Mo Shen, Lu Chen, Luan Huai, Cong Huang, Hailiang Wu, Xi Yang, Chao Ma, Jingsong Zhou, Wei Du, Huihui Fan, Lingzi He, Lin Wan, Chunling Qin, Shengying |
author_facet | Li, Mo Shen, Lu Chen, Luan Huai, Cong Huang, Hailiang Wu, Xi Yang, Chao Ma, Jingsong Zhou, Wei Du, Huihui Fan, Lingzi He, Lin Wan, Chunling Qin, Shengying |
author_sort | Li, Mo |
collection | PubMed |
description | Schizophrenia (SCZ) is a highly heritable psychiatric disorder that affects approximately 1% of population around the world. However, early relevant studies did not reach clear conclusions of the genetic mechanisms of SCZ, suggesting that additional susceptibility loci that exert significant influence on SCZ are yet to be revealed. So, in order to identify novel susceptibility genes that account for the genetic risk of SCZ, we performed a systematic family-based study using whole exome sequencing (WES) in 65 Han Chinese families. The analysis of 51 SCZ trios with both unaffected parents identified 22 exonic and 1 splice-site de novo mutations (DNMs) on a total of 23 genes, and showed that 12 genes carried rare protein-altering compound heterozygous mutations in more than one trio. In addition, we identified 26 exonic or splice-site single nucleotide polymorphisms (SNPs) on 18 genes with nominal significance (P < 5 × 10(−4)) using a transmission disequilibrium test (TDT) in all the families. Moreover, TDT result confirmed a SCZ susceptibility locus on 3p21.1, encompassing the multigenetic region NEK4-ITIH1-ITIH3-ITIH4. Through several different strategies to predict the potential pathogenic genes in silico, we revealed 4 previous discovered susceptibility genes (TSNARE1, PBRM1, STAB1 and OLIG2) and 4 novel susceptibility loci (PSEN1, TLR5, MGAT5B and SSPO) in Han Chinese SCZ patients. In summary, we identified a list of putative candidate genes for SCZ using a family-based WES approach, thus improving our understanding of the pathology of SCZ and providing critical clues to future functional validation. |
format | Online Article Text |
id | pubmed-7026419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70264192020-03-03 Novel genetic susceptibility loci identified by family based whole exome sequencing in Han Chinese schizophrenia patients Li, Mo Shen, Lu Chen, Luan Huai, Cong Huang, Hailiang Wu, Xi Yang, Chao Ma, Jingsong Zhou, Wei Du, Huihui Fan, Lingzi He, Lin Wan, Chunling Qin, Shengying Transl Psychiatry Article Schizophrenia (SCZ) is a highly heritable psychiatric disorder that affects approximately 1% of population around the world. However, early relevant studies did not reach clear conclusions of the genetic mechanisms of SCZ, suggesting that additional susceptibility loci that exert significant influence on SCZ are yet to be revealed. So, in order to identify novel susceptibility genes that account for the genetic risk of SCZ, we performed a systematic family-based study using whole exome sequencing (WES) in 65 Han Chinese families. The analysis of 51 SCZ trios with both unaffected parents identified 22 exonic and 1 splice-site de novo mutations (DNMs) on a total of 23 genes, and showed that 12 genes carried rare protein-altering compound heterozygous mutations in more than one trio. In addition, we identified 26 exonic or splice-site single nucleotide polymorphisms (SNPs) on 18 genes with nominal significance (P < 5 × 10(−4)) using a transmission disequilibrium test (TDT) in all the families. Moreover, TDT result confirmed a SCZ susceptibility locus on 3p21.1, encompassing the multigenetic region NEK4-ITIH1-ITIH3-ITIH4. Through several different strategies to predict the potential pathogenic genes in silico, we revealed 4 previous discovered susceptibility genes (TSNARE1, PBRM1, STAB1 and OLIG2) and 4 novel susceptibility loci (PSEN1, TLR5, MGAT5B and SSPO) in Han Chinese SCZ patients. In summary, we identified a list of putative candidate genes for SCZ using a family-based WES approach, thus improving our understanding of the pathology of SCZ and providing critical clues to future functional validation. Nature Publishing Group UK 2020-01-16 /pmc/articles/PMC7026419/ /pubmed/32066673 http://dx.doi.org/10.1038/s41398-020-0708-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Li, Mo Shen, Lu Chen, Luan Huai, Cong Huang, Hailiang Wu, Xi Yang, Chao Ma, Jingsong Zhou, Wei Du, Huihui Fan, Lingzi He, Lin Wan, Chunling Qin, Shengying Novel genetic susceptibility loci identified by family based whole exome sequencing in Han Chinese schizophrenia patients |
title | Novel genetic susceptibility loci identified by family based whole exome sequencing in Han Chinese schizophrenia patients |
title_full | Novel genetic susceptibility loci identified by family based whole exome sequencing in Han Chinese schizophrenia patients |
title_fullStr | Novel genetic susceptibility loci identified by family based whole exome sequencing in Han Chinese schizophrenia patients |
title_full_unstemmed | Novel genetic susceptibility loci identified by family based whole exome sequencing in Han Chinese schizophrenia patients |
title_short | Novel genetic susceptibility loci identified by family based whole exome sequencing in Han Chinese schizophrenia patients |
title_sort | novel genetic susceptibility loci identified by family based whole exome sequencing in han chinese schizophrenia patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026419/ https://www.ncbi.nlm.nih.gov/pubmed/32066673 http://dx.doi.org/10.1038/s41398-020-0708-y |
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