title: High frequencies of de novo CNVs in bipolar disorder and schizophrenia.
abstract: While it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n = 185), schizophrenia (n = 177), and healthy controls (n = 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR = 4.8 [1.4,16.0], p = 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR = 6.3 [1.7,22.6], p = 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR = 5.0 [1.5,16.8], p = 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases.
authors.affiliation: Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Malhotra
authors.forename: Shane
authors.initials: S
authors.lastname: McCarthy
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Michaelson
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vacic
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Burdick
authors.forename: Seungtai
authors.initials: S
authors.lastname: Yoon
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Aiden
authors.initials: A
authors.lastname: Corvin
authors.forename: Sydney
authors.initials: S
authors.lastname: Gary
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Gershon
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Maria
authors.initials: M
authors.lastname: Karayiorgou
authors.forename: John R
authors.initials: JR
authors.lastname: Kelsoe
authors.forename: Olga
authors.initials: O
authors.lastname: Krastoshevsky
authors.forename: Verena
authors.initials: V
authors.lastname: Krause
authors.forename: Ellen
authors.initials: E
authors.lastname: Leibenluft
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Levy
authors.forename: Vladimir
authors.initials: V
authors.lastname: Makarov
authors.forename: Abhishek
authors.initials: A
authors.lastname: Bhandari
authors.forename: Anil K
authors.initials: AK
authors.lastname: Malhotra
authors.forename: Francis J
authors.initials: FJ
authors.lastname: McMahon
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: James B
authors.initials: JB
authors.lastname: Potash
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sebat
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult