Genetic underpinnings of white matter ‘connectivity’: Heritability, risk, and heterogeneity in schizophrenia

Voineskos, Aristotle N.

doi:10.1016/j.schres.2014.03.034

Cited by 39 publications

(27 citation statements)

References 121 publications

(129 reference statements)

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“…Although the detailed molecular events during SZ progression remain elusive, it is widely accepted that abnormalities in early brain development caused by inherited genetic variants alter critical developmental and maturational processes, resulting in eventual emergence of disabling psychoses[31–33]. A plethora of genes have polymorphisms associated with SZ [9, 34–38].…”

Section: Discussionmentioning

confidence: 99%

Association of ARHGAP18 polymorphisms with schizophrenia in the Chinese-Han population

et al. 2017

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Numerous developmental genes have been linked to schizophrenia (SZ) by case-control and genome-wide association studies, suggesting that neurodevelopmental disturbances are major pathogenic mechanisms. However, no neurodevelopmental deficit has been definitively linked to SZ occurrence, likely due to disease heterogeneity and the differential effects of various gene variants across ethnicities. Hence, it is critical to examine linkages in specific ethnic populations, such as Han Chinese. The newly identified RhoGAP ARHGAP18 is likely involved in neurodevelopment through regulation of RhoA/C. Here we describe four single nucleotide polymorphisms (SNPs) in ARHGAP18 associated with SZ across a cohort of >2000 cases and controls from the Han population. Two SNPs, rs7758025 and rs9483050, displayed significant differences between case and control groups both in genotype (P = 0.0002 and P = 7.54×10−6) and allelic frequencies (P = 4.36×10−5 and P = 5.98×10−7), respectively. The AG haplotype in rs7758025−rs9385502 was strongly associated with the occurrence of SZ (P = 0.0012, OR = 0.67, 95% CI = 0.48–0.93), an association that still held following a 1000-times random permutation test (P = 0.022). In an independently collected validation cohort, rs9483050 was the SNP most strongly associated with SZ. In addition, the allelic frequencies of rs12197901 remained associated with SZ in the combined cohort (P = 0.021), although not in the validation cohort alone (P = 0.251). Collectively, our data suggest the ARHGAP18 may confer vulnerability to SZ in the Chinese Han population, providing additional evidence for the involvement of neurodevelopmental dysfunction in the pathogenesis of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Association of ARHGAP18 polymorphisms with schizophrenia in the Chinese-Han population

et al. 2017

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“…Individual susceptibility to schizophrenia varies even with the same environmental exposure. Therefore, genetic susceptibility has evoked researchers' interest [64], and studies focusing on polymorphisms of genes in the pathogenesis of schizophrenia are increasing in number. SNP of the DRD2 gene are one of the most widely studied factors in the etiology of schizophrenia due to their central roles in dopaminergic pathways.…”

Section: Discussionmentioning

confidence: 99%

The -141C Ins/Del and Taq1A polymorphism in the dopamine D2 receptor gene may confer susceptibility to schizophrenia in Asian populations

Wang¹,

Liu

Xin

et al. 2016

Journal of Clinical Neuroscience

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“…A bioinformatics analysis of predicted and validated miR-137 target genes revealed a significant enrichment of these genes within the axonal guidance canonical pathway [1]. One target, ZNF804A , is a well-known schizophrenia candidate gene [25] that has been linked to reduced integrity of the corpus callosum [26], although its relationship to white matter integrity has varied across studies [27; 28]. Since many other miR-137 target genes are also schizophrenia risk genes [1], the role of these genes in white matter development and morphology lends support to our finding of MIR137HGrv genotype-by-diagnosis—rather than just genotype—effects on corpus callosum volume.…”

Section: Discussionmentioning

confidence: 99%

MIR137HG risk variant rs1625579 genotype is related to corpus callosum volume in schizophrenia

Patel

Kelly

Wright

et al. 2015

Neuroscience Letters

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Genome-wide association studies implicate the MIR137HG risk variant rs1625579 (MIR137HGrv) within the host gene for microRNA-137 as a potential regulator of schizophrenia susceptibility. We examined the influence of MIR137HGrv genotype on 17 subcortical and callosal volumes in a large sample of individuals with schizophrenia and healthy controls (n=841). Although the volumes were overall reduced relative to healthy controls, for individuals with schizophrenia the homozygous MIR137HGrv risk genotype was associated with attenuated reduction of mid-posterior corpus callosum volume (p=0.001), along with trend-level effects in the adjacent central and posterior corpus callosum. These findings are unique in the literature and remain robust after analysis in ethnically homogenous and single-scanner subsets of the larger sample. Thus, our study suggests that the mechanisms whereby MIR137HGrv works to increase schizophrenia risk are not those that generate the corpus callosum volume reductions commonly found in the disorder.

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Genetic underpinnings of white matter ‘connectivity’: Heritability, risk, and heterogeneity in schizophrenia

Cited by 39 publications

References 121 publications

Association of ARHGAP18 polymorphisms with schizophrenia in the Chinese-Han population

Association of ARHGAP18 polymorphisms with schizophrenia in the Chinese-Han population

The -141C Ins/Del and Taq1A polymorphism in the dopamine D2 receptor gene may confer susceptibility to schizophrenia in Asian populations

MIR137HG risk variant rs1625579 genotype is related to corpus callosum volume in schizophrenia

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