门德尔的随机化有助于识别精神分裂症风险增强剂RNAs
Linyan Ye1,2,3, Chaoying Ni1, Renhao Chen1
1Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Molecular psychiatry
|November 23, 2025
概括
这项研究通过分析遗传数据,揭示了与精神分裂症风险相关的增强器RNA (eRNA). 一个特定的eRNA,RGS6e,促进神经元分化,可能降低精神分裂症风险.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 增强子RNAs (eRNAs) 表明增强子活性,但它们的调节机制尚不清楚.
- 了解eRNA的功能对于阐明复杂疾病的发病因子至关重要.
研究的目的:
- 为转录非编码增强子RNA (TNEs) 构建表达量化特征位置 (eQTL) 地图.
- 使用遗传和转录基因数据识别与精神分裂症风险相关的TNE.
- 研究精神分裂症中TNE的调节机制.
主要方法:
- 利用BrainSeq数据,为71,022个TNERNAs创建了祖先分层的eQTL地图.
- 综合精神病学基因组学联盟 (PGC3) 精神分裂症基因组广泛关联研究 (GWAS) 数据与欧洲祖先的eQTL使用基于总结数据的门德尔随机化 (SMR).
- 进行了差异表达 (DE) 分析,并将发现与抑制剂ZNF135水平和RGS6e功能联系起来.
主要成果:
- 确定了61个精神分裂症风险TNE,其中19个重叠DE分析结果.
- 观察到DE和SMR对重叠TNEs的影响之间的反相关性,与相反的表型和基因型贡献相关.
- 与精神分裂症中ZNF135水平降低相关的差异,脱抑动机匹配的TNEs.
- 验证了RGS6e在调节神经系统基因,促进神经元分化和降低精神分裂症风险方面的作用.
结论:
- 基于eQTL的SMR分析对于了解增强剂在精神分裂症风险中的作用至关重要.
- 开发的TNE eQTL地图可以促进精神和神经退行性疾病的研究.
- 增强剂及其转录在疾病发病和进展中起着至关重要的作用.
相关概念视频
Alternative RNA Splicing
24.6K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
24.6K
Genome-wide Association Studies-GWAS
15.2K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
15.2K
Biological Causes of Schizophrenia
468
Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
468
RNA Splicing
60.3K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
60.3K
Single Nucleotide Polymorphisms-SNPs
17.9K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
17.9K
Human Genetics
1.4K
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
1.4K

