Genome-wide survey implicates the influence of copy number variants (CNVs) in the development of early-onset bipolar disorder

Priebe, Lutz; Fa, Degenhardt; Herms, Stefan; Haenisch, Britta; Mattheisen, Manuel; Nieratschker,; Weingarten, Moritz; Witt, Stephanie H.; Breuer, René; Paul, Torsten; Alblas, Margrieta; Moebus, Susanne; Lathrop, Mark; Leboyer, Marion; Schreiber, Stefan; Grigoroiu‐Serbanescu, Maria; Maier, Wolfgang; Propping, Peter; Rietschel, Marcella; Nöthen, Markus M.; Cichon, Sven; Tw, Mühleisen

doi:10.1038/mp.2011.8

Cited by 80 publications

(78 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lastly, we compared our CNV results to findings in the previous studies of BPD [7,24,28,29,30,31,32,33]. We found that five of the 1005 selected CNV regions (6q16.3, 6q27, 9q34.3, and two regions on 19p12) were also identified in previous studies (see Table 5).…”

Section: Resultssupporting

confidence: 57%

See 1 more Smart Citation

Identifying Potential Regions of Copy Number Variation for Bipolar Disorder

Chen

Hung

et al. 2014

Microarrays

View full text Add to dashboard Cite

Bipolar disorder is a complex psychiatric disorder with high heritability, but its genetic determinants are still largely unknown. Copy number variation (CNV) is one of the sources to explain part of the heritability. However, it is a challenge to estimate discrete values of the copy numbers using continuous signals calling from a set of markers, and to simultaneously perform association testing between CNVs and phenotypic outcomes. The goal of the present study is to perform a series of data filtering and analysis procedures using a DNA pooling strategy to identify potential CNV regions that are related to bipolar disorder. A total of 200 normal controls and 200 clinically diagnosed bipolar patients were recruited in this study, and were randomly divided into eight control and eight case pools. Genome-wide genotyping was employed using Illumina Human Omni1-Quad array with approximately one million markers for CNV calling. We aimed at setting a series of criteria to filter out the signal noise of marker data and to reduce the chance of false-positive findings for CNV regions. We first defined CNV regions for each pool. Potential CNV regions were reported based on the different patterns of CNV status between cases and controls. Genes that were mapped into the potential CNV regions were examined with association testing, Gene Ontology enrichment analysis, and checked with existing literature for their associations with bipolar disorder. We reported several CNV regions that are related to bipolar disorder. Two CNV regions on chromosome 11 and 22 showed significant signal differences between cases and controls (p < 0.05). Another five CNV regions on chromosome 6, 9, and 19 were overlapped with results in previous CNV studies. Experimental validation of two CNV regions lent some support to our reported findings. Further experimental and replication studies could be designed for these selected regions.

show abstract

Section: Resultssupporting

confidence: 57%

“…Priebe et al . found a CNV region at 6q27 that was overrepresented in bipolar patients with age at onset ≤21 [28]. This region was also reported to be enriched in affected members of a three-generation Amish pedigree of European descent [29].…”

Section: Resultsmentioning

confidence: 99%

Identifying Potential Regions of Copy Number Variation for Bipolar Disorder

Chen

Hung

et al. 2014

Microarrays

View full text Add to dashboard Cite

show abstract

“…In support of a neurodevelopmental etiology metaanalytic imaging studies show reduced brain volume of the whole brain, the hippocampus and the amygdala in SZ; the evidence for such changes in brain morphology is less consistent in BPD [Murray et al, 2004]. Priebe et al [2012] could find no increased CNV burden in BPD patients overall, but did find an increased burden in the subgroup of young onset (<21 years) patients, again consistent with a strong neurodevelopmental influence of rare CNVs.…”

Section: Discussionmentioning

confidence: 57%

Rare copy number variants in neuropsychiatric disorders: Specific phenotype or not?

Bossche

Johnstone

Stražišar

et al. 2012

American J of Med Genetics Pt B

View full text Add to dashboard Cite

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 (1-2%) 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.

show abstract

“…These alterations, such as copy number variations (CNVs), are likely to be rare but to have a larger effect on risk for developing BD compared with the common SNPs identified through GWAS. Although only a few studies of rare variation have been conducted in BD, the evidence suggests that there is an enrichment of rare CNVs in patients with BD compared with controls (70)(71)(72). However, the effects reported are small, and it appears that CNVs do not play as large of a role in the development of BD as they do in the development of schizophrenia or autism spectrum disorders (70), where structural variation appears to play a larger role.…”

Section: Structural Genetic Alterationsmentioning

confidence: 64%

The Neurobiology of Bipolar Disorder: Neuroimaging and Genetics Update

Mahon¹,

Russo²,

Perez‐Rodriguez³

et al. 2015

FOC

View full text Add to dashboard Cite

disorder is a heterogeneous, complex, multidimensional neuropsychiatric condition characterized by episodes of (hypo)mania and depression. The neurobiology of bipolar disorder is undoubtedly complicated, and much remains to be discovered regarding the neural and genetic correlates of this disorder. In the present work, we present an update on what is currently known regarding the neurobiology of bipolar disorder with a focus on data from neuroimaging and genetic studies. Magnetic resonance imaging studies suggest alterations in both the structure and function of prefrontal and cortical regions implicated in emotion regulation and cognition. Genetic studies have identified several risk variants for the disorder, yet the functional relevance of these variants remains to be clarified. Future studies that take into account the phenotypic heterogeneity of bipolar disorder are likely to advance our understanding of the neurobiology of this complicated neuropsychiatric illness.

show abstract

Genome-wide survey implicates the influence of copy number variants (CNVs) in the development of early-onset bipolar disorder

Cited by 80 publications

References 49 publications

Identifying Potential Regions of Copy Number Variation for Bipolar Disorder

Identifying Potential Regions of Copy Number Variation for Bipolar Disorder

Rare copy number variants in neuropsychiatric disorders: Specific phenotype or not?

The Neurobiology of Bipolar Disorder: Neuroimaging and Genetics Update

Contact Info

Product

Resources

About