Genetics of schizophrenia from a clinicial perspective

Kukshal, Prachi; Thelma, B.K.; Nimgaonkar, Vishwajit L.; Deshpande, Smita N.

doi:10.3109/09540261.2012.709178

Cited by 11 publications

(4 citation statements)

References 182 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In past two decades, a number of hypothesis-driven candidate gene variations, focused mainly on genes from the neurotransmitter and signaling pathways, were tested for their association with SZ, as well as tardive dyskinesia, cognition and response to antipsychotic drugs in the Indian population (Table 1 ). The sample size in these studies varied (see reviews 34 , 35 ). Of these, the most significant associations were observed for rs715505 ( p = 0.00007) in synaptogyrin-1 36 ; and those with SNPs in NRG1 were replicated 37 , 38 (Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

Attempts to replicate genetic associations with schizophrenia in a cohort from north India

et al. 2017

Self Cite

View full text Add to dashboard Cite

Schizophrenia is a chronic, severe, heritable disorder. Genome-wide association studies, conducted predominantly among Caucasians, have indicated > 100 risk alleles, with most significant SNPs on chromosome 6. There is growing interest as to whether these risk alleles are relevant in other ethnic groups as well. Neither an Indian genome-wide association studies nor a systematic replication of GWAS findings from other populations are reported. Thus, we analyzed 32 SNPs, including those associated in the Caucasian ancestry GWAS and other candidate gene studies, in a north Indian schizophrenia cohort (n = 1009 patients; n = 1029 controls) using a Sequenom mass array. Cognitive functioning was also assessed using the Hindi version of the Penn Computerized Neuropsychological Battery in a subset of the sample. MICB (rs6916394) a previously noted Caucasian candidate, was associated with schizophrenia at the p = 0.02 level. One SNP, rs2064430, AHI1 (6q23.3, SZ Gene database SNP) was associated at the p = 0.04 level. Other candidates had even less significance with rs6932590, intergenic (p = 0.07); rs3130615, MICB (p = 0.08); rs6916921, NFKBIL1 (p = 0.08) and rs9273012, HLA-DQA1 (p = 0.06) and haplotypic associations (p = 0.01–0.05) of 6p SNPs were detected. Of note, nominally significant associations with cognitive variables were identified, after covarying for age and diagnostic status. SNPs with p < 0.01 were: rs3130375, with working memory (p = 0.007); rs377763, with sensorimotor (p = 0.004); rs6916921, NFKBIL1 with emotion (p = 0.01). This relative lack of significant positive associations is likely influenced by the sample size and/or differences in the genetic architecture of schizophrenia across populations, encouraging population specific studies to identify shared and unique genetic risk factors for schizophrenia.

show abstract

Section: Introductionmentioning

confidence: 99%

Attempts to replicate genetic associations with schizophrenia in a cohort from north India

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although widely studied, the pathophysiology and molecular mechanisms of schizophrenia remain unclear. Linkage and association analyses have identified many potential genetic risk factors for schizophrenia (Kukshal et al., 2012). The disorder is probably because of the altered expression of a number of genes that interact at the level of biological pathways or gene networks.…”

Section: Introductionmentioning

confidence: 99%

Schizophrenia risk candidate EGR3 is a novel transcriptional regulator of RELN and regulates neurite outgrowth via the Reelin signal pathway in vitro

Nie

Zhang

et al. 2020

Journal of Neurochemistry

View full text Add to dashboard Cite

Schizophrenia is a severe psychiatric disorder with a strong hereditary component that affects approximately 1% of the world's population. The disease is most likely caused by the altered expression of a number of genes that function at the level of biological pathways or gene networks. Transcription factors (TF) are indispensable regulators of gene expression. EGR3 is a TF associated with schizophrenia. In the current study, DNA microarray and ingenuity pathway analyses (IPA) demonstrated that EGR3 regulates Reelin signaling pathway in SH‐SY5Y cells. ChIP and luciferase reporter studies confirmed that EGR3 directly binds to the promoter region of RELN thereby activating RELN expression. The expression of both EGR3 and RELN was decreased during neuronal differentiation induced by retinoic acid (RA) in SH‐SY5Y cells, and EGR3 over‐expression reduced neurite outgrowth which could be partially reversed by the knockdown of RELN. The expression levels of EGR3 and RELN in peripheral blood of subjects with schizophrenia were found to be down‐regulated (compared with healthy controls), and were positively correlated. Furthermore, data mining from public databases revealed that the expression levels of EGR3 and RELN were presented a positive correlation in post‐mortem brain tissue of subjects with schizophrenia. Taken together, this study suggests that EGR3 is a novel TF of the RELN gene and regulates neurite outgrowth via the Reelin signaling pathway. Our findings contribute to the understanding of the regulatory role of EGR3 in the pathophysiology and molecular mechanisms of schizophrenia, and potentially to the development of new therapies and diagnostic biomarkers for the disorder.

show abstract

“…The disease is characterized by positive symptoms, such as delusions, hallucinations, and thought disorder, and by negative symptoms, such as social withdrawal, apathy, and cognitive impairment. Family, adoption, and twin studies have consistently demonstrated a substantial genetic influence on the development of schizophrenia, with inherited risk estimates in the range of 80% (Cannon, 2005;Kukshal et al, 2012). Previous studies have suggested that polymorphisms in the regulator of G-protein signaling 9 (RGS9) may be related to schizophrenia (Liou et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Regulators of G-protein signaling 9 genetic variations in Chinese subjects with schizophrenia

Zhu

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. To identify single-nucleotide polymorphisms that contribute to the genetic susceptibility to schizophrenia, we examined the potential association between schizophrenia and 9 single nucleotide polymorphisms (rs1530351, rs4791230, rs2869577, rs8077696, rs8070231, rs2292592, rs9916525, rs1122079, and rs4790953) in the G-protein signaling 9 gene. The participants included 395 schizophrenia subjects and 400 healthy controls. The selected single nucleotide polymorphisms were genotyped using mass spectrometry techniques. The allelic or genotypic frequencies of the rs4791230 (promoter region) polymorphisms in subjects with schizophrenia were significantly different from those in healthy controls. The subjects with schizophrenia had a significantly higher frequency of the G allele (P = 0.030, odds ratio = 1.589, 95% confidence interval = 1.042-2.422) of rs4791230. Strong linkage disequilibrium was observed in 4 blocks 8459 SNPs of RGS9 in schizophrenia ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 8458-8465 (2015) (D' > 0.9). Significantly fewer T-A (rs1530351-rs4791230) haplotypes (P = 0.029) were found in subjects with schizophrenia. These findings suggest a role of G-protein signaling 9 polymorphisms in schizophrenia among Han Chinese and may be informative for future genetic or neurobiological studies on schizophrenia.

show abstract

Genetics of schizophrenia from a clinicial perspective

Cited by 11 publications

References 182 publications

Attempts to replicate genetic associations with schizophrenia in a cohort from north India

Attempts to replicate genetic associations with schizophrenia in a cohort from north India

Schizophrenia risk candidate EGR3 is a novel transcriptional regulator of RELN and regulates neurite outgrowth via the Reelin signal pathway in vitro

Regulators of G-protein signaling 9 genetic variations in Chinese subjects with schizophrenia

Contact Info

Product

Resources

About