Gene expression and association analyses of LIM (PDLIM5) in bipolar disorder and schizophrenia

Kato, Takeshi; Iwayama, Yoshimi; Kakiuchi, Chihiro; Iwamoto, Kazuya; Yamada, Kazuo; Minabe, Yoshio; Nakamura, Kazuhiko; Mori, Norio; Fujii, Kumiko; Nanko, Shinichiro; Yoshikawa, Takeo

doi:10.1038/sj.mp.4001719

Cited by 55 publications

(50 citation statements)

References 37 publications

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“…our finding of strong gene cluster contribution for UBE3A in schizophrenia is intriguing in view of multiple reports that genomic imprinting may play a role in disease etiology (VeenstraVanderWeele et al 1999;Nurmi et al 2001;Jiang et al 2004). Gene expression and association analyses of PDLIM5 (which for us lies in the overlap between bipolar disorder and schizophrenia) suggest its involvement in the etiology of bipolar disorder and schizophrenia (Kato et al 2005), and RAPGEF4 (in the bipolar disorder and autism overlap genes) has been related to the autistic phenotype (Bacchelli et al 2003). Intriguingly, many of our candidate genes have been analyzed in relation to Alzheimer's disease: BLMH (Nivet-Antoine et al 2003); MAPK8IP1 (Helbecque et al 2003); MAPKAPK2 (Culbert et al 2006); LPL (Blain et al 2006); NEFM (Wang et al 2002); FRK (Watanabe et al 2004); and KCNIP3 (Jin et al 2005).…”

Section: Genome Research 1155mentioning

confidence: 87%

Genetic-linkage mapping of complex hereditary disorders to a whole-genome molecular-interaction network

Iossifov¹,

Tian²,

Baron³

et al. 2008

Genome Res.

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Common hereditary neurodevelopmental disorders such as autism, bipolar disorder, and schizophrenia are most likely both genetically multifactorial and heterogeneous. Because of these characteristics traditional methods for genetic analysis fail when applied to such diseases. To address the problem we propose a novel probabilistic framework that combines the standard genetic linkage formalism with whole-genome molecular-interaction data to predict pathways or networks of interacting genes that contribute to common heritable disorders. We apply the model to three large genotype–phenotype data sets, identify a small number of significant candidate genes for autism (24), bipolar disorder (21), and schizophrenia (25), and predict a number of gene targets likely to be shared among the disorders.

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Section: Genome Research 1155mentioning

confidence: 87%

Genetic-linkage mapping of complex hereditary disorders to a whole-genome molecular-interaction network

Iossifov¹,

Tian²,

Baron³

et al. 2008

Genome Res.

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“…Previous genetic association studies of PDLIM5 SNP rs2433320 showed significant association in BPD [18], schizophrenia [16] and major depression [17].…”

Section: Discussionmentioning

confidence: 99%

“…The involvement of PDLIM5 in mental disorders was supported by genetic association studies that relate several polymorphisms on PDLIM5 with mental disorders. For examples, the single nucleotide polymorphism (SNP) rs2433320 is associated with schizophrenia [16], major depression [17] and BPD [18][19][20]. Moreover, PDLIM5 SNP rs2433322 has been found associated with schizophrenia [17] whereas another SNP, rs2438146 is associated with BPD in its allelic frequencies but not genotype frequencies [18].…”

Section: Introductionmentioning

confidence: 99%

“…For examples, the single nucleotide polymorphism (SNP) rs2433320 is associated with schizophrenia [16], major depression [17] and BPD [18][19][20]. Moreover, PDLIM5 SNP rs2433322 has been found associated with schizophrenia [17] whereas another SNP, rs2438146 is associated with BPD in its allelic frequencies but not genotype frequencies [18]. In addition, a previous study showed that rs2433322 and rs2438146 did not associate with BPD in its own, but the haplotypes constructed from three SNPs of rs2433320-rs2438146-rs2433322 were significantly associated with BPD [20].…”

Section: Introductionmentioning

confidence: 99%

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Genetic association study of PDLIM5 and HTR2A variants in Malaysian subjects diagnosed with bipolar disorder; a genetic modelling approach

et al. 2018

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Genetic hereditary has been implicated in bipolar disorder pathogenesis. The PDLIM5 and HTR2A genes have been investigated for its association with bipolar disorder in various populations, however, the results have been conflicting. In this study, we investigate the association between bipolar disorder and the two genes of interest, PDLIM5 and HTR2A genes. We recruited 253 bipolar disorder patients (75 Malays, 104 Chinese, and 74 Indians) and 505 control individuals (198 Malays, 155 Chinese, and 152 Indians) from three ethnic groups within Malaysian population. We genotyped for 3 SNPs of the PDLIM5 (rs2433320, rs2433322 and rs2438146) and 3 SNPs of the HTR2A (rs6313, rs2070040 and rs6311). Significant associations between bipolar disorder and each of the 3 SNPs of PDLIM5 in Malays, Indians and pooled samples. However, only rs2438146 remains significant in the Malays as co-dominant (T/T vs. C/C, p=0.004, OR=0.128, 95%CI=0.031-0.524) and recessive genetic models (T/T vs. C/T+C/C, p=0.003, OR=0.122, 95%CI=0.030-0.494) after applying conservative Bonferroni correction. Haplotype analysis of 3 SNPs of PDLIM5 also showed a significant association with bipolar disorder. No association was observed between bipolar disorder and each of the 3 SNPs of HTR2A in any of the ethnicities. We conclude that PDLIM5 polymorphisms are associated with bipolar disorder in the pooled analysis. After stratification to different ethnic groups, the association remains significant in the Malay and Indian groups. The association is also supported by the significant association in haplotype analysis of PDLIM5. We also conclude there is no association between the HTR2A polymorphisms in the Malaysian population.

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“…Several lines of evidence suggest PDLIM5 as a candidate gene for both schizophrenia (SZ) and bipolar disorder (BP). First, PDLIM5 is significantly upregulated in postmortem brains of patients with SZ or BP from the Stanley Medical Research Institute's (SMRI) brain collections (Iwamoto et al, 2004b;Kato et al, 2005) and abnormally expressed in the peripheral leukocytes derived from patients with each disorder (Iwamoto et al, 2004a;Numata et al, 2007). Second, PDLIM5 is an adopter protein interacting with N-type calcium channel (Maeno-Hikichi et al, 2003), a signaling pathway implicated in the pathophysiology of BP (Warsh et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

PDLIM5 and susceptibility to bipolar disorder: a family-based association study and meta-analysis

Shi

Badner

Liu

2008

Psychiatric Genetics

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Objectives-The postsynaptic density-95/discs large/zone occludens-1 (PDZ) domain and LIM (Lin-11, Isl-1, and Mec-3) domain 5 (PDLIM5) gene has been analyzed as a candidate gene for both schizophrenia (SZ) and bipolar disorder (BP) in Japanese samples. We performed a family-based association study to test the hypothesis that variants in PDLIM5 increase susceptibility to BP in European Americans and a meta-analysis to clarify whether there is a single marker consistently contributing to risk for BP.Methods-Five single nucleotide polymorphisms (SNPs) in the PDLIM5 gene were genotyped in 290 European American BP families. Programs Sibling-Transmission/Disequilibrium Test (sib_tdt) and PDTPHASE were used for allelic and haplotypic association, respectively. We carried out a meta-analysis combing our family-based data and case-control data from two Japanese sample sets and from two genome-wide association (GWA) studies.Results-Our association analysis showed no single SNP associated with BP. A rare haplotype consisted of rs10008257 and rs2433320 had nominal association (p = 0.045), which failed to survive correction for multiple tests. The meta-analysis identified a significant allelic association at rs2433320 in all combined samples (excluding overlapped samples in GWA: overall OR = 0.897, 95% CI: 0.838-0.961, adjusted p = 0.012) and in all Caucasian samples (excluding overlapped samples in GWA: overall OR = 0.905, 95% CI: 0.843-0.971, adjusted p = 0.032), but not in the Japanese samples.Conclusion-PDLIM5 may play a minor effect on susceptibility to bipolar disorder in Caucasians. The findings in Japanese need further confirmation in larger independent samples.

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Gene expression and association analyses of LIM (PDLIM5) in bipolar disorder and schizophrenia

Cited by 55 publications

References 37 publications

Genetic-linkage mapping of complex hereditary disorders to a whole-genome molecular-interaction network

Genetic-linkage mapping of complex hereditary disorders to a whole-genome molecular-interaction network

Genetic association study of PDLIM5 and HTR2A variants in Malaysian subjects diagnosed with bipolar disorder; a genetic modelling approach

PDLIM5 and susceptibility to bipolar disorder: a family-based association study and meta-analysis

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