Association study of a single nucleotide polymorphism in brain cytoplasmic 200 long-noncoding RNA and psychiatric disorders

Kahaei, Mir Salar; Ghafouri‐Fard, Soudeh; Namvar, Amir; Omrani, Mir Davood; Sayad, Arezou

doi:10.1007/s11011-020-00582-7

Cited by 12 publications

(7 citation statements)

References 18 publications

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“… 6 Actually, these ncRNAs have a direct effect on mRNA translation, splicing, and export from nucleus. 7 In addition, lncRNAs are also involved in various pathophysiological mechanisms of CNS diseases and targeting these lncRNAs is able to treat most of these diseases, 8 , 9 , 10 such as Alzheimer’s disease, 11 and ischemic stroke. 12 Furthermore, lncRNAs have specific expression profiles in brain tissue but also can be used as potential independent prognostic molecular markers.…”

Section: Introductionmentioning

confidence: 99%

Expression Profiles of Long Non-coding RNA and Messenger RNA in Human Traumatic Brain Injury

Ren

Chen

Cao

et al. 2020

Molecular Therapy - Nucleic Acids

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Long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) play an important role in central nervous diseases; however, the exact expression and co-expressed profiles in human traumatic brain injury (TBI) are still unknown. Therefore, we investigated whole blood in 12 patients with TBI and 4 healthy controls to observe expression characteristics with different severity. We identified 3,035 lncRNAs and 1,204 mRNAs differentially expressed in the severe TBI group, 2,362 lncRNAs and 656 mRNAs in the moderate group, and 433 lncRNAs and 100 mRNAs in the mild group. Enrichment analyses showed 30 signaling pathways such as inflammatory and immune response pathways. Subsequently, a lncRNA-gene co-expression network was generated for 717 lncRNA-mRNA pairs and most of them with a positive correlation. Based on GSEA analysis, we found that TBI caused severe immune abnormality reflected on Th1, Th2, and Th17 cell differentiation deficiency. Finally, the expression of one upregulated and one downregulated lncRNA was validated in all three TBI groups, which was consistent with the microarray results. In summary, our results show that expression profiles of lncRNAs and mRNAs are significantly different in bloods from different severity TBI especially in immune response, providing novel insight for lncRNAs in human TBI.

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Section: Introductionmentioning

confidence: 99%

Expression Profiles of Long Non-coding RNA and Messenger RNA in Human Traumatic Brain Injury

Ren

Chen

Cao

et al. 2020

Molecular Therapy - Nucleic Acids

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“…The gene‐based analysis showed that three lncRNAs ( STXBP5 ‐ AS1 , LINC01247 , and LINC00534 ) were also associated with ADHD symptoms ( p < 0.007) 15 . One SNP rs4404327 which located in a neuron‐specific lncRNA ( BC200 RNA ) was also found to be associated with ADHD in an Iranian population 16 . However, none of the above analyses have adopted the RDoC approach to probe beyond the ADHD clinical phenotypes, such as on executive function and brain structural integrity as potential endophenotypes more proximal to gene‐molecule mechanisms.…”

Section: Introductionmentioning

confidence: 97%

A potential association of RNF219‐AS1 with ADHD: Evidence from categorical analysis of clinical phenotypes and from quantitative exploration of executive function and white matter microstructure endophenotypes

Chen

et al. 2021

CNS Neurosci Ther

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Aims Attention‐deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder of substantial heritability, yet emerging evidence suggests that key risk variants might reside in the noncoding regions of the genome. Our study explored the association of lncRNAs (long noncoding RNAs) with ADHD as represented at three different phenotypic levels guided by the Research Domain Criteria (RDoC) framework: (i) ADHD caseness and symptom dimension, (ii) executive functions as functional endophenotype, and (iii) potential genetic influence on white matter architecture as brain structural endophenotype. Methods Genotype data of 107 tag single nucleotide polymorphisms (SNP) from 10 candidate lncRNAs were analyzed in 1040 children with ADHD and 630 controls of Chinese Han descent. Executive functions including inhibition and set‐shifting were assessed by STROOP and trail making tests, respectively. Imaging genetic analyses were performed in a subgroup of 33 children with ADHD and 55 controls using fractional anisotropy (FA). Results One SNP rs3908461 polymorphism in RNF219‐AS1 was found to be significantly associated with ADHD caseness: with C‐allele detected as the risk genotype in the allelic model (P = 8.607E‐05) and dominant genotypic model (P = 9.628E‐05). Nominal genotypic effects on inhibition (p = 0.020) and set‐shifting (p = 0.046) were detected. While no direct effect on ADHD core symptoms was detected, mediation analysis suggested that SNP rs3908461 potentially exerted an indirect effect through inhibition function [B = 0.21 (SE = 0.12), 95% CI = 0.02‐0.49]. Imaging genetic analyses detected significant associations between rs3908461 genotypes and FA values in corpus callosum, left superior longitudinal fasciculus, left posterior limb of internal capsule, left posterior thalamic radiate (include optic radiation), and the left anterior corona radiate (P FWE corrected < 0.05). Conclusion Our present study examined the potential roles of lncRNA in genetic etiological of ADHD and provided preliminary evidence in support of the potential RNF219‐AS1 involvement in the pathophysiology of ADHD in line with the RDoC framework.

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“…The resulting barcode counts from RNA-seq inform lncRNA sequences that influence nuclear localization, which in turn affects the regulatory activity of the lncRNA [ 45 ]. Subcellular localization provides valuable insight into the function of lncRNAs, which is unknown compared to protein coding genes despite evidence found for their role in brain development and neurodevelopmental disorders such as ASD, Rett’s syndrome, attention-deficit hyperactivity disorder (ADHD), and schizophrenia [ 79 – 92 ] and other neurological disorders such as Alzheimer’s, Parkinson’s, and Huntington’s disease [ 82 , 93 ].…”

Section: Introductionmentioning

confidence: 99%

Focus on your locus with a massively parallel reporter assay

McAfee

Bell

Krupa

et al. 2022

J Neurodevelop Disord

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A growing number of variants associated with risk for neurodevelopmental disorders have been identified by genome-wide association and whole genome sequencing studies. As common risk variants often fall within large haplotype blocks covering long stretches of the noncoding genome, the causal variants within an associated locus are often unknown. Similarly, the effect of rare noncoding risk variants identified by whole genome sequencing on molecular traits is seldom known without functional assays. A massively parallel reporter assay (MPRA) is an assay that can functionally validate thousands of regulatory elements simultaneously using high-throughput sequencing and barcode technology. MPRA has been adapted to various experimental designs that measure gene regulatory effects of genetic variants within cis- and trans-regulatory elements as well as posttranscriptional processes. This review discusses different MPRA designs that have been or could be used in the future to experimentally validate genetic variants associated with neurodevelopmental disorders. Though MPRA has limitations such as it does not model genomic context, this assay can help narrow down the underlying genetic causes of neurodevelopmental disorders by screening thousands of sequences in one experiment. We conclude by describing future directions of this technique such as applications of MPRA for gene-by-environment interactions and pharmacogenetics.

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Association study of a single nucleotide polymorphism in brain cytoplasmic 200 long-noncoding RNA and psychiatric disorders

Cited by 12 publications

References 18 publications

Expression Profiles of Long Non-coding RNA and Messenger RNA in Human Traumatic Brain Injury

Expression Profiles of Long Non-coding RNA and Messenger RNA in Human Traumatic Brain Injury

A potential association of RNF219‐AS1 with ADHD: Evidence from categorical analysis of clinical phenotypes and from quantitative exploration of executive function and white matter microstructure endophenotypes

Focus on your locus with a massively parallel reporter assay

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