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| 2. |
- Van Den Bossche, Maarten J., et al.
(författare)
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Identification of a CACNA2D4 deletion in late onset bipolar disorder patients and implications for the involvement of voltage-dependent calcium channels in psychiatric disorders
- 2012
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Ingår i: American Journal of Medical Genetics Part B. - : Wiley. - 1552-4841 .- 1552-485X. ; 159B:4, s. 465-475
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Tidskriftsartikel (refereegranskat)abstract
- The GWAS-based association of CACNA1C with bipolar disorder (BPD) is one of the strongest genetic findings to date. CACNA1C belongs to the family of CACN genes encoding voltage-dependent calcium channels (VDCCs). VDCCs are involved in brain circuits and cognitive processes implicated in BPD and schizophrenia (SZ). Recently, it was shown that rare copy number variations (CNVs) are found at an increased frequency in SZ and to a lesser extent also in BPD, suggesting the involvement of CNVs in the causation of these diseases. We hypothesize that CNVs in CACN genes can influence the susceptibility to BPD, SZ, and/or schizoaffective disorder (SZA). A search for CNVs in eight CACN genes in a patient-control sample of European decent was performed. A total of 709 BP patients, 645 SZ patients, 189 SZA patients, and 1,470 control individuals were screened using the Multiplex Amplicon Quantification (MAQ) method. We found a rare, partial deletion of 35.7?kb in CACNA2D4 in two unrelated late onset bipolar I patients and in one control individual. All three deletions shared the same breakpoints removing exons 1726 of CACNA2D4, comprising part of the CACHE domain. Based on the data we cannot claim causality to BPD of the identified CACNA2D4 deletion but nevertheless this deletion can be important in unraveling the underlying processes leading to psychiatric diseases in general and BPD in particular.
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| 3. |
- Van Den Bossche, Maarten J., et al.
(författare)
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Rare copy number variants in neuropsychiatric disorders : Specific phenotype or not?
- 2012
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Ingår i: American Journal of Medical Genetics Part B. - : Wiley. - 1552-4841 .- 1552-485X. ; 159B:7, s. 812-822
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Tidskriftsartikel (refereegranskat)abstract
- From a number of genome-wide association studies it was shown that de novo and/or rare copy number variants (CNVs) are found at an increased frequency in neuropsychiatric diseases. In this study we examined the prevalence of CNVs in six genomic regions (1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, and 16p11.2) previously implicated in neuropsychiatric diseases. Hereto, a cohort of four neuropsychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, and intellectual disability) and control individuals from three different populations was used in combination with Multilpex Amplicon Quantifiaction (MAQ) assays, capable of high resolution (kb range) and custom-tailored CNV detection. Our results confirm the etiological candidacy of the six selected CNV regions for neuropsychiatric diseases. It is possible that CNVs in these regions can result in disturbed brain development and in this way lead to an increased susceptibility for different neuropsychiatric disorders, dependent on additional genetic and environmental factors. Our results also suggest that the neurodevelopmental component is larger in the etiology of schizophrenia and intellectual disability than in mood disorders. Finally, our data suggest that deletions are in general more pathogenic than duplications. Given the high frequency of the examined CNVs (12%) in patients of different neuropsychiatric disorders, screening of large cohorts with an affordable and feasible method like the MAQ assays used in this study is likely to result in important progress in unraveling the genetic factors leading to an increased susceptibility for several psychiatric disorders.
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| 4. |
- Van Den Eede, Filip, et al.
(författare)
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Single nucleotide polymorphism analysis of corticotropin-releasing factor-binding protein gene in recurrent major depressive disorder.
- 2007
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Ingår i: Psychiatry Research. ; 153
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Tidskriftsartikel (refereegranskat)abstract
- Corticotropin-releasingfactor-bindingprotein(CRF-BP) regulates the availability of freeCRFandisafunctional candidate gene for affective disorders. Previous research showed an association between polymorphisms in the CRF-BPgene and recurrent major depression(MDD) in a Swedish sample. The purpose of the current study was to re-evaluate the previous findings in an extended Swedish sample and in an independent Belgian sample of patients with recurrent MDD and in control samples. In total, 317 patients and 696 control individuals were included. Five single nucleotide polymorphisms (SNPs) and a deletionpolymorphismintheCRF-BP gene were genotyped and the haplotype block structure of the gene was assessed. Intheextended Swedish population, there was a trend towards an association between two SNPs and MDD. The subsequent gender analysis showed significant associations of three SNPs (CRF-BPs2T;CRF-BPs11TandCRF-BPs12C) and haplotype G_T_C_T_C with MDD in Swedish males. However, these findings did not withstand correction for multiple testing and there were nosignificant SNP or haplotype associations in the Belgian MDD sample. In conclusion, this study does not provide confirmatory evidence for a role of the CRF-BPgene in the vulnerability for MDD in general. The association between genetic CRF-BP variants and MDD may be sexually dimorphic, but this issue requires further investigation in a larger sample.
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| 5. |
- Van Den Eede, Filip, et al.
(författare)
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Single nucleotide polymorphism analysis of corticotropin-releasing factor-binding protein gene in recurrent major depressive disorder
- 2007
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 153:1, s. 17-25
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Tidskriftsartikel (refereegranskat)abstract
- Corticotropin-releasing factor-binding protein (CRF-BP) regulates the availability of free CRF and is a functional candidate gene for affective disorders. Previous research showed an association between polymorphisms in the CRF-BP gene and recurrent major depression (MDD) in a Swedish sample. The purpose of the current study was to re-evaluate the previous findings in an extended Swedish sample and in an independent Belgian sample of patients with recurrent MDD and in control samples. In total, 317 patients and 696 control individuals were included. Five single nucleotide polymorphisms (SNPs) and a deletion polymorphism in the CRF-BP gene were genotyped and the haplotype block structure of the gene was assessed. In the extended Swedish population, there was a trend towards an association between two SNPs and MDD. The subsequent gender analysis showed significant associations of three SNPs (CRF-BPs2 T; CRF-BPs11 T and CRF-BPs12 C) and haplotype G_T_C_T_C with MDD in Swedish males. However, these findings did not withstand correction for multiple testing and there were no significant SNP or haplotype associations in the Belgian MDD sample. In conclusion, this study does not provide confirmatory evidence for a role of the CRF-BP gene in the vulnerability for MDD in general. The association between genetic CRF-BP variants and MDD may be sexually dimorphic, but this issue requires further investigation in a larger sample.
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