Identification of rare and common variants in BNIP3L: a schizophrenia susceptibility gene

BACKGROUND: Schizophrenia is a chronic and severe mental disorder, and it has been predicted to be highly polygenic. Common SNPs located in or near BNIP3L were found to be genome-wide significantly associated with schizophrenia in recent genome-wide association studies. The purpose of our study is t...

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Autores principales: Zhou, Juan, Ma, Chuanchuan, Wang, Ke, Li, Xiuli, Jian, Xuemin, Zhang, Han, Yuan, Jianmin, Yin, Jiajun, Chen, Jianhua, Shi, Yongyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212671/
https://www.ncbi.nlm.nih.gov/pubmed/32393399
http://dx.doi.org/10.1186/s40246-020-00266-4
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author Zhou, Juan
Ma, Chuanchuan
Wang, Ke
Li, Xiuli
Jian, Xuemin
Zhang, Han
Yuan, Jianmin
Yin, Jiajun
Chen, Jianhua
Shi, Yongyong
author_facet Zhou, Juan
Ma, Chuanchuan
Wang, Ke
Li, Xiuli
Jian, Xuemin
Zhang, Han
Yuan, Jianmin
Yin, Jiajun
Chen, Jianhua
Shi, Yongyong
author_sort Zhou, Juan
collection PubMed
description BACKGROUND: Schizophrenia is a chronic and severe mental disorder, and it has been predicted to be highly polygenic. Common SNPs located in or near BNIP3L were found to be genome-wide significantly associated with schizophrenia in recent genome-wide association studies. The purpose of our study is to investigate potential causal variants in BNIP3L gene. RESULTS: We performed targeted sequencing for all exons and un-translated regions of BNIP3L gene among 1806 patients with schizophrenia and 998 healthy controls of Han Chinese origin. Three rare nonsynonymous mutations, BNIP3L (NM_004331): c.52A>G, c.167G>A and c.313A>T, were identified in schizophrenia cases, and two of them were newly reported. The frequencies of these rare nonsynonymous mutations were significantly different between schizophrenia cases and healthy controls. For the common variants, rs147389989 achieved significance in both allelic and genotypic distributions with schizophrenia. Rs1042992 and rs17310286 were significantly associated with schizophrenia in meta-analyses using PGC, CLOZUK, and our new datasets in this study. CONCLUSIONS: Our findings provided further evidence that BNIP3L gene is a susceptibility gene of schizophrenia and revealed functional and potential causal mutations in BNIP3L. However, more functional validations are suggested to better understand the role of BNIP3L in the etiology of schizophrenia.
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spelling pubmed-72126712020-05-18 Identification of rare and common variants in BNIP3L: a schizophrenia susceptibility gene Zhou, Juan Ma, Chuanchuan Wang, Ke Li, Xiuli Jian, Xuemin Zhang, Han Yuan, Jianmin Yin, Jiajun Chen, Jianhua Shi, Yongyong Hum Genomics Primary Research BACKGROUND: Schizophrenia is a chronic and severe mental disorder, and it has been predicted to be highly polygenic. Common SNPs located in or near BNIP3L were found to be genome-wide significantly associated with schizophrenia in recent genome-wide association studies. The purpose of our study is to investigate potential causal variants in BNIP3L gene. RESULTS: We performed targeted sequencing for all exons and un-translated regions of BNIP3L gene among 1806 patients with schizophrenia and 998 healthy controls of Han Chinese origin. Three rare nonsynonymous mutations, BNIP3L (NM_004331): c.52A>G, c.167G>A and c.313A>T, were identified in schizophrenia cases, and two of them were newly reported. The frequencies of these rare nonsynonymous mutations were significantly different between schizophrenia cases and healthy controls. For the common variants, rs147389989 achieved significance in both allelic and genotypic distributions with schizophrenia. Rs1042992 and rs17310286 were significantly associated with schizophrenia in meta-analyses using PGC, CLOZUK, and our new datasets in this study. CONCLUSIONS: Our findings provided further evidence that BNIP3L gene is a susceptibility gene of schizophrenia and revealed functional and potential causal mutations in BNIP3L. However, more functional validations are suggested to better understand the role of BNIP3L in the etiology of schizophrenia. BioMed Central 2020-05-11 /pmc/articles/PMC7212671/ /pubmed/32393399 http://dx.doi.org/10.1186/s40246-020-00266-4 Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Zhou, Juan
Ma, Chuanchuan
Wang, Ke
Li, Xiuli
Jian, Xuemin
Zhang, Han
Yuan, Jianmin
Yin, Jiajun
Chen, Jianhua
Shi, Yongyong
Identification of rare and common variants in BNIP3L: a schizophrenia susceptibility gene
title Identification of rare and common variants in BNIP3L: a schizophrenia susceptibility gene
title_full Identification of rare and common variants in BNIP3L: a schizophrenia susceptibility gene
title_fullStr Identification of rare and common variants in BNIP3L: a schizophrenia susceptibility gene
title_full_unstemmed Identification of rare and common variants in BNIP3L: a schizophrenia susceptibility gene
title_short Identification of rare and common variants in BNIP3L: a schizophrenia susceptibility gene
title_sort identification of rare and common variants in bnip3l: a schizophrenia susceptibility gene
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212671/
https://www.ncbi.nlm.nih.gov/pubmed/32393399
http://dx.doi.org/10.1186/s40246-020-00266-4
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