MLC1 Gene Is Associated with Schizophrenia and Bipolar Disorder in Southern India

Verma, Ranjana; Mukerji, Mitali; Grover, Deepak; B-Rao, Chandrika; Das, Swapan K.; Kubendran, Shobana; Jain, Sanjeev; Brahmachari, Samir K.

doi:10.1016/j.biopsych.2005.03.027

Cited by 44 publications

(18 citation statements)

References 39 publications

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“…[35][36][37] Interestingly, a recent study of a Southern Indian population reported evidence of association between MLC1 and both SZ and BPD. 38 According to the regional LD pattern discussed above it does not seem likely that the Indian MLC1 signal and the present BRD1 association represent the same susceptibility locus, unless the population of Southern India has a different and more extended LD pattern. However, this might actually be the case as the Indian study also reported association between both disorders and the marker D22S1161, which is located more than 1 cM proximal to BRD1 and MLC1 (http://www.ncbi.nlm.nih.gov/mapview/).…”

Section: Discussionmentioning

confidence: 84%

Evidence implicating BRD1 with brain development and susceptibility to both schizophrenia and bipolar affective disorder

et al. 2006

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Linkage studies suggest that chromosome 22q12-13 may contain one or more shared susceptibility genes for schizophrenia (SZ) and bipolar affective disorder (BPD). In a Faeroese sample, we previously reported association between microsatellite markers located at 22q13.31-qtel and both disorders. The present study reports an association analysis across five genes (including 14 single nucleotide and two microsatellite polymorphisms) in this interval using a case-control sample of 162 BPD, 103 SZ patients and 200 controls. The bromodomain-containing 1 gene (BRD1), which encodes a putative regulator of transcription showed association with both disorders with minimal P-values of 0.0046 and 0.00001 for single marker and overall haplotype analysis, respectively. A specific BRD1 2-marker 'risk' haplotype showed a frequency of B10% in the combined case group versus B1% in controls (P-value 2.8 Â 10 À7 ). Expression analysis of BRD1 mRNA revealed widespread expression in mammalian brain tissue, which was substantiated by immunohistochemical detection of BRD1 protein in the nucleus, perikaryal cytosol and proximal dendrites of the neurons in the adult rat, rabbit and human CNS. Quantitative mRNA analysis in developing fetal pig brain revealed spatiotemporal differences with high expression at early embryonic stages, with intense nuclear and cytosolar immunohistochemical staining of the neuroepithelial layer and early neuroblasts, whilst more mature neurons at later embryonic stages had less nuclear staining. The results implicate BRD1 with SZ and BPD susceptibility and provide evidence that suggests a role for BRD1 in neurodevelopment.

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Section: Discussionmentioning

confidence: 84%

Evidence implicating BRD1 with brain development and susceptibility to both schizophrenia and bipolar affective disorder

et al. 2006

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“…The case-control sample set analyzed in this study is ethnically quite homogenous, being of south Indian origin. Further details of the study cohort are described elsewhere (Verma et al 2005). …”

Section: Study Populationmentioning

confidence: 99%

SYNGR1 is associated with schizophrenia and bipolar disorder in southern India

et al. 2005

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Chromosome 22q11-13 is one of the most consistent linkage regions for schizophrenia (SCZ) and bipolar disorder (BPAD). The SYNGR1 gene, which is associated with presynaptic vesicles in neuronal cells, is located on 22q13.1. We have previously identified a novel nonsense mutation in the SYNGR1 gene in a SCZ pedigree. In the present study, a detailed analysis of this gene was performed in a case-control cohort (198 BPAD, 193 SCZ and 107 controls from southern India) to test for association with SCZ and BPAD. Sequence analysis of all exonic and flanking intronic regions of the SYNGR1 gene in 198 BPAD and 193 SCZ cases revealed a novel mutation Lsy99Glu (in one BPAD patient) and two other novel common polymorphisms [synonymous single nucleotide polymorphism (SNP-Ser97Ser) and an Asn ins/del] in the SYNGR1 gene. We also validated 9 out of 14 dbSNPs in our population. Case-control analysis revealed allelic (P=0.028-0.00007) association of five polymorphisms with SCZ and/or BPAD cases. Further, 3-SNP (with LD block 1 SNPs) and 2-SNP (with LD block 2 SNPs) haplotype analyses did not show any association with either SCZ or BPAD. Our results support SYNGR1 as a probable susceptibility gene for SCZ and BPAD. Also, the observed association of SYNGR1 with both SCZ and BPAD suggests the likely involvement of a common pathway in the etiology of these disorders.

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“…On the other hand, rs2235349 is marked as '++PolyDoms++', because this SNP is tightly linked to some SNP in the PolyDoms database that is classified as deleterious or damaging. Thus, the association between rs2235349 and schizophrenia (Verma, et al, 2005) might result from another nearby SNP that is more causative.…”

Section: Evaluating Predicted Properties Of the Snpsmentioning

confidence: 99%