A functional missense variant in ITIH3 affects protein expression and neurodevelopment and confers schizophrenia risk in the Han Chinese population

KIZ OpenIR > 科研部门 > 疾病机理遗传学和进化医学学科组（姚永刚）

	A functional missense variant in ITIH3 affects protein expression and neurodevelopment and confers schizophrenia risk in the Han Chinese population
	Li, Kaiqin; Li, Yifan; Wang, Junyang; Huo, Yongxia; Huang, Di; Li, Shiwu; Liu, Jiewei; Li, Xiaoyan; Liu, Rong; Chen, Xiaogang; Yao, Yong-Gang; Chen, Ceshi; Xiao, Xiao; Li, Ming; Luo, Xiong-Jian
	2020
发表期刊	JOURNAL OF GENETICS AND GENOMICS
ISSN	1673-8527
卷号	47 期号:5 页码:233-248
摘要	The Psychiatric Genomics Consortium (PGC) has recently identified 10 potential functional coding variants for schizophrenia. However, how these coding variants confer schizophrenia risk remains largely unknown. Here, we investigate the associations between eight potential functional coding variants identified by PGC and schizophrenia in a large Han Chinese sample (n = 4022 cases and 9270 controls). Among the eight tested single nucelotide polymorphisms (SNPs), rs3617 (a missense variant, p.K315Q in the ITIH3 gene) showed genome-wide significant association with schizophrenia in the Han Chinese population (P=8.36 x 10(-16)), with the same risk allele as in PGC. Interestingly, rs3617 is located in a genomic region that is highly evolutionarily conserved, and its schizophrenia risk allele (C allele) was associated with lower ITIH3 mRNA and protein expression. Intriguingly, mouse neural stem cells stably overexpressing ITIH3 with different alleles of rs3617 exhibited significant differences in proliferation, migration, and differentiation, suggesting the impact of rs3617 on neurodevelopment. Subsequent transcriptome analysis found that the differentially expressed genes in neural stem cells stably over-expressing different alleles of rs3617 were significantly enriched in schizophrenia-related pathways, including cell adhesion, synapse assembly, MAPK and PI3K-AKT pathways. Our study provides conver- gent lines of evidence suggesting that rs3617 in ITIH3 likely affects protein function and neurodevelopment and thereby confers risk of schizophrenia. Copyright (C) 2020, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/12761
专题	科研部门_疾病机理遗传学和进化医学学科组（姚永刚）
推荐引用方式 GB/T 7714	Li, Kaiqin,Li, Yifan,Wang, Junyang,et al. A functional missense variant in ITIH3 affects protein expression and neurodevelopment and confers schizophrenia risk in the Han Chinese population[J]. JOURNAL OF GENETICS AND GENOMICS,2020,47(5):233-248.
APA	Li, Kaiqin.,Li, Yifan.,Wang, Junyang.,Huo, Yongxia.,Huang, Di.,...&Luo, Xiong-Jian.(2020).A functional missense variant in ITIH3 affects protein expression and neurodevelopment and confers schizophrenia risk in the Han Chinese population.JOURNAL OF GENETICS AND GENOMICS,47(5),233-248.
MLA	Li, Kaiqin,et al."A functional missense variant in ITIH3 affects protein expression and neurodevelopment and confers schizophrenia risk in the Han Chinese population".JOURNAL OF GENETICS AND GENOMICS 47.5(2020):233-248.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2021110320.pdf（4445KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文