Involvement of the long intergenic non-coding RNA LINC00461 in schizophrenia

Objective LINC00461 is a highly conserved intergenic non-protein coding RNA that was implicated in schizophrenia at the genome-wide level. We aim to explore potential mechanisms underlying the involvement of LINC00461 in schizophrenia. Methods We performed a meta-analysis to investigate the associat...

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Vydáno v:BMC psychiatry Ročník 22; číslo 1; s. 59 - 7
Hlavní autoři: Rao, Shuquan, Tian, Lin, Cao, Hongbao, Baranova, Ancha, Zhang, Fuquan
Médium: Journal Article
Jazyk:angličtina
Vydáno: London BioMed Central 26.01.2022
BioMed Central Ltd
Springer Nature B.V
BMC
Témata:
Alleles
Brain
Brain mapping
Consortia
Development and progression
Ethics
Etiology
fMRI
Functional magnetic resonance imaging
Gene expression
Genetic aspects
Genetic Predisposition to Disease
Genomes
Genomics
Genotype & phenotype
Health aspects
Health risk assessment
Hippocampus
Hippocampus - metabolism
Humans
Independent sample
LINC00461
Medicine
Medicine & Public Health
Memory
Mental disorders
Neuroimaging
Non-coding RNA
Nuclear family
Pathogenesis
Physiological aspects
Polymorphism, Single Nucleotide
Psychiatry
Psychotherapy
Regulatory sequences
RNA
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Schizophrenia
Schizophrenia - genetics
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Software
Statistical analysis
Transcription
China
United States > US
Schizophrenia
fMRI
LINC00461
Hippocampus
ISSN:1471-244X, 1471-244X
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Shrnutí:Objective LINC00461 is a highly conserved intergenic non-protein coding RNA that was implicated in schizophrenia at the genome-wide level. We aim to explore potential mechanisms underlying the involvement of LINC00461 in schizophrenia. Methods We performed a meta-analysis to investigate the association of LINC00461 rs410216 with schizophrenia, and evaluate the effects of the rs410216 on hippocampal volume and function using the functional magnetic resonance imaging (fMRI) analysis. We utilized the GTEx dataset to profile the expression distribution of LINC00461 across different brain regions, and to investigate the potential impact of the risk SNPs on the expression of LINC00461 and other nearby genes. We compared blood expression levels of LINC00461 between schizophrenia patients and controls. Results Here we show that single-nucleotide polymorphisms (SNPs) located in regulatory elements spanning the LINC00461 region are significantly associated with schizophrenia (index SNP rs410216, P meta  = 1.43E-05); subjects carrying the risk allele of rs410216 showed decreased hippocampal volume. However, no significant association of the rs410216 variant with hippocampal activation was observed. Moreover, the expression level of LINC00461 mRNA was significantly lower in first-onset schizophrenia patients, and the risk allele also predicts a lower transcriptional level of LINC00461 in the hippocampus. Conclusion Together, these convergent lines of evidence implicate inadequate LINC00461 expression in the hippocampus in the development of schizophrenia, providing novel insight into the genetic architecture and biological etiology of schizophrenia.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1471-244X
1471-244X
DOI:10.1186/s12888-022-03718-4