title: Singleton deletions throughout the genome increase risk of bipolar disorder.
abstract: An overall burden of rare structural genomic variants has not been reported in bipolar disorder (BD), although there have been reports of cases with microduplication and microdeletion. Here, we present a genome-wide copy number variant (CNV) survey of 1001 cases and 1034 controls using the Affymetrix single nucleotide polymorphism (SNP) 6.0 SNP and CNV platform. Singleton deletions (deletions that appear only once in the dataset) more than 100 kb in length are present in 16.2% of BD cases in contrast to 12.3% of controls (permutation P=0.007). This effect was more pronounced for age at onset of mania <or=18 years old. Our results strongly suggest that BD can result from the effects of multiple rare structural variants.
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: Y
authors.initials: Y
authors.lastname: Qian
authors.forename: N
authors.initials: N
authors.lastname: Alliey-Rodriguez
authors.forename: J R
authors.initials: JR
authors.lastname: Kelsoe
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authors.initials: T
authors.lastname: Greenwood
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authors.initials: C
authors.lastname: Nievergelt
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authors.initials: TB
authors.lastname: Barrett
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authors.initials: R
authors.lastname: McKinney
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authors.lastname: Schork
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authors.initials: EN
authors.lastname: Smith
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authors.lastname: Bloss
authors.forename: J
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authors.lastname: Nurnberger
authors.forename: H J
authors.initials: HJ
authors.lastname: Edenberg
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authors.lastname: Foroud
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authors.initials: W
authors.lastname: Sheftner
authors.forename: W B
authors.initials: WB
authors.lastname: Lawson
authors.forename: E A
authors.initials: EA
authors.lastname: Nwulia
authors.forename: M
authors.initials: M
authors.lastname: Hipolito
authors.forename: W
authors.initials: W
authors.lastname: Coryell
authors.forename: J
authors.initials: J
authors.lastname: Rice
authors.forename: W
authors.initials: W
authors.lastname: Byerley
authors.forename: F
authors.initials: F
authors.lastname: McMahon
authors.forename: T G
authors.initials: TG
authors.lastname: Schulze
authors.forename: W
authors.initials: W
authors.lastname: Berrettini
authors.forename: J B
authors.initials: JB
authors.lastname: Potash
authors.forename: P L
authors.initials: PL
authors.lastname: Belmonte
authors.forename: P P
authors.initials: PP
authors.lastname: Zandi
authors.forename: M G
authors.initials: MG
authors.lastname: McInnis
authors.forename: S
authors.initials: S
authors.lastname: Zöllner
authors.forename: D
authors.initials: D
authors.lastname: Craig
authors.forename: S
authors.initials: S
authors.lastname: Szelinger
authors.forename: D
authors.initials: D
authors.lastname: Koller
authors.forename: S L
authors.initials: SL
authors.lastname: Christian
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.forename: E S
authors.initials: ES
authors.lastname: Gershon
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012306:Risk; D017384:Sequence Deletion / Q000235:genetics*