Singleton deletions throughout the genome increase risk of bipolar disorder

Zhang, Dandan; Cheng, Lijun; Qian, Yu; Alliey‐Rodriguez, Ney; Kelsoe, John R.; Greenwood, Tiffany A.; Nievergelt, Caroline M.; Barrett, Thomas B.; McKinney, R. Anne; Schork, Nicholas J.; Smith, Erin N.; Bloss, Cinnamon S.; Nürnberger, John I.; Edenberg, Howard J.; Foroud, Tatiana; Sheftner, William; Lawson, William B.; Nwulia, Evaritus A.; Hipolito, Maria; Coryell, William; Rice, John P.; Byerley, William; McMahon, Francis J.; Schulze, Thomas G.; Berrettini, Wade H.; Potash, James B.; Belmonte, Pamela L.; Zandi, Peter P.; McInnis, Melvin G.; Zöllner, Sebastian; Craig, David W.; Szelinger, Szabolics; Koller, Daniel L.; Christian, Susan L.; Liu, Chun Yu; Gershon, Elliot S.

doi:10.1038/mp.2008.144

Cited by 135 publications

(146 citation statements)

References 25 publications

Supporting

Mentioning

127

Contrasting

Order By: Relevance

“…Individuals with PD did not have an increased genome-wide rare CNV burden. The number of rare CNVs was estimated to be smaller than that of the previous study 19 on the basis of global burden analysis, because CNVs were considered to be colocalized and identical in the present study if they overlapped by at least 50% of their length.…”

Section: Discussionmentioning

confidence: 77%

“…19,23,29 CNVs were classified as rare (found in o1% of the total sample) or common (found in X5%). They were considered to be colocalized if they overlapped by at least 50% of their length, as implemented in PLINK.…”

Section: Discussionmentioning

confidence: 99%

“…Sex chromosomes were removed from the analysis, as they are incorrectly segmented by Birdsuite 19 and PennCNV. 21 Bonferroni-corrected P-values o0.5 were considered significant.…”

Section: Discussionmentioning

confidence: 99%

“…The values of RATE and PROP were lower than those of the previous study. 19 CNVs were considered to be colocalized and identical if they overlapped by at least 50% of their length. The number of rare CNVs was consequently estimated to be comparatively low in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…The results of the SNP genome-wide association study are described elsewhere. 17 CNVs were determined with Birdsuite software 18 version 1.5.5 over the thresholds of logarithm of odds X10, 18,19 the number of probes in CNV X10 18,20,21 and individual CNVs o300. A total of 906 600 SNP probes and 946 000 CNV non-polymorphic probes on the chip were genotyped at the University of Tokyo, Graduate School of Medicine, according to the manufacturer's protocol.…”

Section: Cnv Detection and Determinationmentioning

confidence: 99%

See 4 more Smart Citations

A genome-wide CNV association study on panic disorder in a Japanese population

Kawamura¹,

Otowa

Koike

et al. 2011

J Hum Genet

View full text Add to dashboard Cite

Family and twin studies have indicated that genetic factors have an important role in panic disorder (PD), whereas its pathogenesis has remained elusive. We conducted a genome-wide copy number variation (CNV) association study to elucidate the involvement of structural variants in the etiology of PD. The participants were 2055 genetically unrelated Japanese people (535 PD cases and 1520 controls). CNVs were detected using Genome-Wide Human SNP array 6.0, determined by Birdsuite and confirmed by PennCNV. They were classified as rare CNVs (found in o1% of the total sample) or common CNVs (found in X5%). PLINK was used to perform global burden analysis for rare CNVs and association analysis for common CNVs. The sample yielded 2039 rare CNVs and 79 common CNVs. Significant increases in the rare CNV burden in PD cases were not found. Common duplications in 16p11.2 showed Bonferroni-corrected P-values o0.05. Individuals with PD did not exhibit an increased genome-wide rare CNV burden. Common duplications were associated with PD and found in the pericentromeric region of 16p11.2, which had been reported to be rich in low copy repeats and to harbor developmental disorders, neuropsychiatric disorders and dysmorphic features. Keywords: 16p11.2; copy number variation; deletion; duplication; genome-wide association study; global burden analysis; Japanese; panic disorder INTRODUCTION Panic disorder (PD) is characterized by recurrent and unexpected panic attacks, subsequent anticipatory anxiety and phobic avoidance, with the frequent development of agoraphobia. 1 The lifetime prevalence of PD is 4.7% with female preponderance. 2 PD frequently takes a chronic course, with many remissions and relapses. 3 Genetic epidemiological researches including family and twin studies have shown that genetic as well as environmental factors have an important role in the pathogenesis of PD. First-degree relatives of proband with PD have a six-fold increased risk of developing the condition. 4 Twin studies show that about 40% of liability toward PD relates to heritable factors. 5 Although several linkage studies and many association studies on more than 350 candidate genes for PD have been concluded, the results were inconsistent, negative or not clearly replicated. 6 Copy number variations (CNVs) are quantitative structural variants; they are deletions and duplications of DNA segments ranging

show abstract

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

“…Sex chromosomes were removed from the analysis, as they are incorrectly segmented by Birdsuite 19 and PennCNV. 21 Bonferroni-corrected P-values o0.5 were considered significant.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cnv Detection and Determinationmentioning

confidence: 99%

See 3 more Smart Citations

A genome-wide CNV association study on panic disorder in a Japanese population

Kawamura¹,

Otowa

Koike

et al. 2011

J Hum Genet

View full text Add to dashboard Cite

show abstract

Rare Copy Number Variants<subtitle>A Point of Rarity in Genetic Risk for Bipolar Disorder and Schizophrenia</subtitle><alt-title>Rare Copy Number Variants</alt-title>

Grozeva

Kirov²,

Ivanov³

et al. 2010

Arch Gen Psychiatry

179

160

View full text Add to dashboard Cite

Schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific CNVs in particular. Our data are consistent with the possibility that possession of large, rare deletions may modify the phenotype in those at risk of psychosis: those possessing such events are more likely to be diagnosed as having schizophrenia, and those without them are more likely to be diagnosed as having bipolar disorder.

show abstract

Copy Number Variations and Neuropsychiatric Diseases

Alliey‐Rodriguez

Gershon

2014

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Copy number variants (CNVs) are submicroscopic deletions and duplications of deoxyribonucleic acid (DNA) segments, which can have a high impact on gene expression. Methods to explore CNVs include array comparative genomic hybridisation, single‐nucleotide polymorphism microarrays and whole genome sequencing. Rare CNVs are strongly associated with neuropsychiatric diseases including autism spectrum disorder, schizophrenia, bipolar disorder and disruptions to some specific loci have been related to more than one disorder. The chromosome 22q11.21 deletion is so far the locus identified with the highest risk, 82% for any psychiatric disorder. De novo copy number events, those present in cases but not in their parents, also have a significant risk for any of these disorders, with an overall risk of 13% to develop a neuropsychiatric disorder if present anywhere in the genome. Key Concepts: Copy number variants are so far the most potent sources of genetic risk for neuropsychiatric disease. Rare and de novo events are associated with neuropsychiatric disorders.

show abstract

Singleton deletions throughout the genome increase risk of bipolar disorder

Cited by 135 publications

References 25 publications

A genome-wide CNV association study on panic disorder in a Japanese population

A genome-wide CNV association study on panic disorder in a Japanese population

Rare Copy Number Variants<subtitle>A Point of Rarity in Genetic Risk for Bipolar Disorder and Schizophrenia</subtitle><alt-title>Rare Copy Number Variants</alt-title>

Copy Number Variations and Neuropsychiatric Diseases

Contact Info

Product

Resources

About