title: Genome-wide survey implicates the influence of copy number variants (CNVs) in the development of early-onset bipolar disorder.
abstract: We used genome-wide single nucleotide polymorphism (SNP) data to search for the presence of copy number variants (CNVs) in 882 patients with bipolar disorder (BD) and 872 population-based controls. A total of 291 (33%) patients had an early age-at-onset < or =21 years (AO < or =21 years). We systematically filtered for CNVs that cover at least 30 consecutive SNPs and which directly affect at least one RefSeq gene. We tested whether (a) the genome-wide burden of these filtered CNVs differed between patients and controls and whether (b) the frequency of specific CNVs differed between patients and controls. Genome-wide burden analyses revealed that the frequency and size of CNVs did not differ substantially between the total samples of BD patients and controls. However, separate analysis of patients with AO < or =21 years and AO>21 years showed that the frequency of microduplications was significantly higher (P=0.0004) and the average size of singleton microdeletions was significantly larger (P=0.0056) in patients with AO < or =21 years compared with controls. A search for specific BD-associated CNVs identified two common CNVs: (a) a 160 kb microduplication on 10q11 was overrepresented in AO < or = 21 years patients (9.62%) compared with controls (3.67%, P=0.0005) and (b) a 248 kb microduplication on 6q27 was overrepresented in the AO< or = 21 years subgroup (5.84%) compared with controls (2.52%, P=0.0039). These data suggest that CNVs have an influence on the development of early-onset, but not later-onset BD. Our study provides further support for previous hypotheses of an etiological difference between early-onset and later-onset BD.
authors.affiliation: Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Priebe
authors.forename: F A
authors.initials: FA
authors.lastname: Degenhardt
authors.forename: S
authors.initials: S
authors.lastname: Herms
authors.forename: B
authors.initials: B
authors.lastname: Haenisch
authors.forename: M
authors.initials: M
authors.lastname: Mattheisen
authors.forename: V
authors.initials: V
authors.lastname: Nieratschker
authors.forename: M
authors.initials: M
authors.lastname: Weingarten
authors.forename: S
authors.initials: S
authors.lastname: Witt
authors.forename: R
authors.initials: R
authors.lastname: Breuer
authors.forename: T
authors.initials: T
authors.lastname: Paul
authors.forename: M
authors.initials: M
authors.lastname: Alblas
authors.forename: S
authors.initials: S
authors.lastname: Moebus
authors.forename: M
authors.initials: M
authors.lastname: Lathrop
authors.forename: M
authors.initials: M
authors.lastname: Leboyer
authors.forename: S
authors.initials: S
authors.lastname: Schreiber
authors.forename: M
authors.initials: M
authors.lastname: Grigoroiu-Serbanescu
authors.forename: W
authors.initials: W
authors.lastname: Maier
authors.forename: P
authors.initials: P
authors.lastname: Propping
authors.forename: M
authors.initials: M
authors.lastname: Rietschel
authors.forename: M M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: S
authors.initials: S
authors.lastname: Cichon
authors.forename: T W
authors.initials: TW
authors.lastname: Mühleisen
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D001714:Bipolar Disorder / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D030541:Databases, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics