Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population

Yu, Hao; Yan, Han; Li, J.; Li, Z.; Zhang, X.; Ma, Yujia; Mei, Ling; Liu, C.; Cai, Lei; Wang, Q.; Zhang, F.; Iwata, Nakao; Ikeda, Masashi; Wang, L.; Lu, Tianlan; Li, M.; Xu, Huji; Wu, Xinyu; Liu, Bowen; Yang, Jianli; Li, K.; Lv, Luxian; Ma, Xin; Wang, C.; Li, L.; Yang, Fu De; Jiang, Tian; Shi, Yongyong; Li, T.; Zhang, Donghui; Yue, Weihua

doi:10.1038/mp.2016.212

Cited by 77 publications

(85 citation statements)

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“…2); rs7596038 is located in the intron region of VRK2 and is predicted to be nonfunctional through the epigenomic analyses using ENCODE data [47], but further studies are necessary to examine its functional impact. Furthermore, in a recent GWAS of SCZ in Han Chinese populations, Yu et al [48] reported that rs1051061 ( r 2 = 0.224 with rs1518395 in Europeans, r 2 = 0.178 with rs1518395 in East Asians) in an exon of VRK2 was genome-wide significantly associated with SCZ in a total of 8,723 cases and 12,813 controls ( p = 1.14 × 10 –12 , see Fig. 1a).…”

Section: Identification Of Vrk2 Variants In Psychiatric Disorders Amomentioning

confidence: 95%

“…For example, it is speculated that reduced Vrk2 levels might induce apoptosis [112, 114], thereby affecting normal neurodevelopment during the early stages of life. In fact, Yu et al [48] recently explored the potential functions of Vrk2 in developing mouse brains. They reported that Vrk2 was expressed in the developing cerebral cortex, and the silencing of Vrk2 resulted in the impairment of multipolar–bipolar neuron transition and neural progenitor proliferation [48].…”

Section: Functions Of Vrk2 In the Neurological Systemmentioning

confidence: 99%

“…In fact, Yu et al [48] recently explored the potential functions of Vrk2 in developing mouse brains. They reported that Vrk2 was expressed in the developing cerebral cortex, and the silencing of Vrk2 resulted in the impairment of multipolar–bipolar neuron transition and neural progenitor proliferation [48]. Therefore, Vrk2 likely plays regulatory roles in cytoskeleton remodeling and progenitor cell recycling/differentiation [48].…”

Section: Functions Of Vrk2 In the Neurological Systemmentioning

confidence: 99%

“…In addition, studies describing the effects of VRK2 on neurodevelopment and brain function are still lacking. Although there is preliminary evidence that this gene may affect neuronal migration [48] and inflammation [115, 159, 160], whether it could affect other aspects of neuronal function, e.g. synaptic development and transmission, is still unclear.…”

Section: Future Perspectivesmentioning

confidence: 99%

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VRK2, a Candidate Gene for Psychiatric and Neurological Disorders

Yue

2018

Complex Psychiatry

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Recent large-scale genetic approaches, such as genome-wide association studies, have identified multiple genetic variations that contribute to the risk of mental illnesses, among which single nucleotide polymorphisms (SNPs) within or near the vaccinia related kinase 2 (VRK2) gene have gained consistent support for their correlations with multiple psychiatric and neurological disorders including schizophrenia (SCZ), major depressive disorder (MDD), and genetic generalized epilepsy. For instance, the genetic variant rs1518395 in VRK2 showed genome-wide significant associations with SCZ (35,476 cases and 46,839 controls, p = 3.43 × 10^–8) and MDD (130,620 cases and 347,620 controls, p = 4.32 × 10^–12) in European populations. This SNP was also genome-wide significantly associated with SCZ in Han Chinese population (12,083 cases and 24,097 controls, p = 3.78 × 10^–13), and all associations were in the same direction of allelic effects. These studies highlight the potential roles of VRK2 in the central nervous system, and this gene therefore might be a good candidate to investigate the shared genetic and molecular basis between SCZ and MDD, as it is one of the few genes known to show genome-wide significant associations with both illnesses. Furthermore, the VRK2 gene was found to be involved in multiple other congenital deficits related to the malfunction of neurodevelopment, adding further support for the involvement of this gene in the pathogenesis of these neurological and psychiatric illnesses. While the precise function of VRK2 in these conditions remains unclear, preliminary evidence suggests that it may affect neuronal proliferation and migration via interacting with multiple essential signaling pathways involving other susceptibility genes/proteins for psychiatric disorders. Here, we have reviewed the recent progress of genetic and molecular studies of VRK2, with an emphasis on its role in psychiatric illnesses and neurological functions. We believe that attention to this important gene is necessary, and further investigations of VRK2 may provide hints into the underlying mechanisms of SCZ and MDD.

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Section: Identification Of Vrk2 Variants In Psychiatric Disorders Amomentioning

confidence: 95%

Section: Functions Of Vrk2 In the Neurological Systemmentioning

confidence: 99%

Section: Functions Of Vrk2 In the Neurological Systemmentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

See 2 more Smart Citations

VRK2, a Candidate Gene for Psychiatric and Neurological Disorders

Yue

2018

Complex Psychiatry

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“…Since 2007, schizophrenia GWAS have been published (for details see http://www.genome.gov/gwastudies). Overall, the studies have failed to support the findings from linkage and candidate gene studies, but the GWAS have instead identified a large number of new susceptibility loci of only very small individual effects—and many of these genomic loci have in fact been replicated in subsequent GWAS and have reached meta-analytic genome-wide significance (see e.g., Shi et al, 2009; Stefansson et al, 2009; Schizophrenia Psychiatric Genome-Wide Association Study Consortium, 2011; Aberg et al, 2013; Ripke et al, 2013; Xiao and Li, 2016; Yu et al, 2016). One seminal study (Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014) combined available schizophrenia GWAS samples into a single analysis and successfully identified 128 independent schizophrenia associations, spanning 108 risk loci of genome-wide significance, 83 of which were novel findings.…”

Section: Molecular Geneticsmentioning

confidence: 99%

Genetics of Schizophrenia: Overview of Methods, Findings and Limitations

Henriksen

Nordgaard

Jansson

2017

Front. Hum. Neurosci.

136

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Genetics constitute a crucial risk factor to schizophrenia. In the last decade, molecular genetic research has produced novel findings, infusing optimism about discovering the biological roots of schizophrenia. However, the complexity of the object of inquiry makes it almost impossible for non-specialists in genetics (e.g., many clinicians and researchers) to get a proper understanding and appreciation of the genetic findings and their limitations. This study aims at facilitating such an understanding by providing a brief overview of some of the central methods and findings in schizophrenia genetics, from its historical origins to its current status, and also by addressing some limitations and challenges that confront this field of research. In short, the genetic architecture of schizophrenia has proven to be highly complex, heterogeneous and polygenic. The disease risk is constituted by numerous common genetic variants of only very small individual effect and by rare, highly penetrant genetic variants of larger effects. In spite of recent advances in molecular genetics, our knowledge of the etiopathogenesis of schizophrenia and the genotype-environment interactions remain limited.

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Novel Risk Loci Associated With Genetic Risk for Bipolar Disorder Among Han Chinese Individuals

Zhang

et al. 2021

JAMA Psychiatry

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IMPORTANCEThe genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood.OBJECTIVE To explore the genetic basis of BD in the Han Chinese population. DESIGN, SETTING, AND PARTICIPANTSA genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020.MAIN OUTCOMES AND MEASURES Single-nucleotide variations with P < 5.00 × 10 −8 were considered to show genome-wide significance of statistical association. RESULTS The HanChinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189[58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 × 10 −8 ; odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (ρ ge = 0.652, SE = 0.106; P = 7.30 × 10 −10 ) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R 2 = 1.27%; P = 1.30 × 10 −19 ) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 × 10 −9 ; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10 −8 ; OR, 0.932; 95% CI, 0.909-0.956).CONCLUSIONS AND RELEVANCE This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.

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Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population

Cited by 77 publications

References 50 publications

<b><i>VRK2</i></b>, a Candidate Gene for Psychiatric and Neurological Disorders

<b><i>VRK2</i></b>, a Candidate Gene for Psychiatric and Neurological Disorders

Genetics of Schizophrenia: Overview of Methods, Findings and Limitations

Novel Risk Loci Associated With Genetic Risk for Bipolar Disorder Among Han Chinese Individuals

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