Evaluation of association of common variants in HTR1A and HTR5A with schizophrenia and executive function

Guan, Fanglin; Lin, Hai; Chen, Gang; Li, Lü; Chen, Teng; Liu, Xinshe; Han, Jaeseok; Li, Tao

doi:10.1038/srep38048

Cited by 47 publications

(24 citation statements)

References 64 publications

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“…The HTR1A rs878567 SNP is located in the 3′-UTR of the 5-HT 1A receptor close to the splice site, and is in strong linkage disequilibrium with the rs6295 promoter polymorphism. 61 The rs878567 polymorphism has been associated with major depression, 46,47 schizophrenia, 194,195 psychosis 196 and depression after childhood physical abuse. 197 While many of these associations are similar to those for rs6295, the association with schizophrenia and psychosis was not as robust for rs6295.…”

Section: Alternative Splicingmentioning

confidence: 99%

Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigm

Albert

François

Vahid-Ansari

2019

jpn

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Major depression and anxiety are highly prevalent and involve chronic dysregulation of serotonin, but they remain poorly understood. Here, we review novel transcriptional (genetic, epigenetic) and posttranscriptional (microRNA, alternative splicing) mechanisms implicated in mental illness, focusing on a key serotonin-related regulator, the serotonin 1A (5-HT 1A) receptor. Functional single-nucleotide polymorphisms and stress-induced DNA methylation of the 5-HT 1A promoter converge to differentially alter pre-and postsynaptic 5-HT 1A receptor expression associated with major depression and reduced therapeutic response to serotonergic antidepressants. Major depression is also associated with altered levels of splice factors and microRNA, posttranscriptional mechanisms that regulate RNA stability. The human 5-HT 1A 3′-untranslated region is alternatively spliced, removing microRNA sites and increasing 5-HT 1A expression, which is reduced in major depression and may be genotype-dependent. Thus, the 5-HT 1A receptor gene illustrates the convergence of genetic, epigenetic and posttranscriptional mechanisms in gene expression, neurodevelopment and neuroplasticity, and major depression. Understanding gene regulatory mechanisms could enhance the detection, categorization and personalized treatment of major depression.

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Section: Alternative Splicingmentioning

confidence: 99%

Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigm

Albert

François

Vahid-Ansari

2019

jpn

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“…Furthermore, HTR2B is also a drug target (Pitychoutis et al, ). Other HTRs that have been less often investigated, but are nevertheless associated with SZ are HTR1B , HTR3A , HTR3B , HTR7 , and HTR5A , which is associated with patient's cognitive abilities (Pal et al, ; Jajodia, Kaur, et al, ; Gupta et al, ; Guan et al, ; Ikeda et al, ). For example, a SZ‐associated promoter SNP rs1062613 C>T in HTR3A (Jajodia, Kaur, et al, ) may affect DNA methylation and CCCTC‐binding factor binding, as this TF binds more strongly to methylated C allele (Jajodia, Singh, et al, ).…”

Section: Serotonin Pathway Genes Associated With Szmentioning

confidence: 99%

Genetic variability of serotonin pathway associated with schizophrenia onset, progression, and treatment

Hrovatin

Kunej

Dolžan

2019

American J of Med Genetics Pt B

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Schizophrenia (SZ) onset and treatment outcome have important genetic components, however individual genes do not have strong effects on SZ phenotype. Therefore, it is important to use the pathway-based approach and study metabolic and signaling pathways, such as dopaminergic and serotonergic. Serotonin pathway has an important role in brain signaling, nevertheless, its role in SZ is not as thoroughly examined as that of dopamine pathway. In this study, we reviewed serotonin pathway genes and genetic variations associated with SZ, including variations at DNA, RNA, and epigenetic level.We obtained 30 serotonin pathway genes from Kyoto encyclopedia of genes and genomes and used these genes for the literature review. We extracted 20 protein coding serotonin pathway genes with genetic variations associated with SZ onset, development, and treatment from 31 research papers. Genes associated with SZ are present on all levels of serotonin pathway: serotonin synthesis, transport, receptor binding, intracellular signaling, and reuptake; however, regulatory genes are poorly researched. We summarized common challenges of genetic association studies and presented some solutions. The analysis of reported serotonin pathway-SZ associations revealed lack of information about certain serotonin pathway genes potentially associated with SZ. Furthermore, it is becoming clear that interactions among serotonin pathway genes and their regulators may bring further knowledge about their involvement in SZ. K E Y W O R D Sgenetic association studies, genetic variations, pharamcogenetics, schizophrenia, serotonin pathway

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“…With the rapid development of high-throughput sequencing, although more and more susceptibility variants of complex diseases have been identified (Guan et al, 2013(Guan et al, , 2014(Guan et al, , 2016a(Guan et al, , 2016b(Guan et al, , 2016cLiu et al, 2014;Zhang et al, 2018a). In recent years, researchers have identified strong association signals between the TLR-9 gene and the risk of KOA in both Han Chinese and Turkish populations (Su et al, 2012a;Balbaloglu et al, 2017;Zheng et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Relationship Between Common Variants in the TLR-9 Gene and Hip Osteoarthritis Susceptibility

Xiao

et al. 2019

Genetic Testing and Molecular Biomarkers

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Objective: Hip osteoarthritis (HOA) is one of the most common types of osteoarthritis and affects nearly 10% of men and 18% of women who are >60 years of age worldwide. It has been demonstrated to be a genetic disease with a 50% heritability risk. Recently, the TLR-9 gene has been associated with knee OA in both Turkish and Chinese populations, but the relationship between the TLR-9 gene and HOA has not been evaluated. In this study, we aimed to evaluate the relationship between the common genetic variants in the TLR-9 gene and the predisposition of Han Chinese individuals to HOA. Methods: A total of 730 HOA patients and 1220 healthy controls were recruited in a hospital-based case-control study. Six common single nucleotide polymorphisms (SNPs) of the TLR-9 gene were selected for genotyping, and genetic association analyses were performed using both single-marker and haplotype-based methods. Results: The SNP rs187084 was found to be significantly associated with the risk of HOA after a Bonferroni correction (adjusted allelic p-values with age, gender, and body mass index [BMI] = 0.0008). The results indicated that the A allele of rs187084 is a risk allele for HOA and is likely to be a predisposing factor leading to an increased risk of HOA (adjusted odds ratio with age, gender, and BMI = 1.26, 95% confidence interval = 1.10-1.43). The results of the haplotype analyses confirmed a similar pattern to the SNP analyses. Conclusions: Our study provides strong evidence that variations in the TLR-9 gene are closely linked with genetic susceptibility to HOA in the Han Chinese population. This finding furthers the role of TLR-9 in the development and occurrence of OA in general.

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Evaluation of association of common variants in HTR1A and HTR5A with schizophrenia and executive function

Cited by 47 publications

References 64 publications

Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigm

Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigm

Genetic variability of serotonin pathway associated with schizophrenia onset, progression, and treatment

Evaluation of the Relationship Between Common Variants in the TLR-9 Gene and Hip Osteoarthritis Susceptibility

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