title: CNV analysis in a large schizophrenia sample implicates deletions at 16p12.1 and SLC1A1 and duplications at 1p36.33 and CGNL1.
abstract: Large and rare copy number variants (CNVs) at several loci have been shown to increase risk for schizophrenia. Aiming to discover novel susceptibility CNV loci, we analyzed 6882 cases and 11 255 controls genotyped on Illumina arrays, most of which have not been used for this purpose before. We identified genes enriched for rare exonic CNVs among cases, and then attempted to replicate the findings in additional 14 568 cases and 15 274 controls. In a combined analysis of all samples, 12 distinct loci were enriched among cases with nominal levels of significance (P < 0.05); however, none would survive correction for multiple testing. These loci include recurrent deletions at 16p12.1, a locus previously associated with neurodevelopmental disorders (P = 0.0084 in the discovery sample and P = 0.023 in the replication sample). Other plausible candidates include non-recurrent deletions at the glutamate transporter gene SLC1A1, a CNV locus recently suggested to be involved in schizophrenia through linkage analysis, and duplications at 1p36.33 and CGNL1. A burden analysis of large (>500 kb), rare CNVs showed a 1.2% excess in cases after excluding known schizophrenia-associated loci, suggesting that additional susceptibility loci exist. However, even larger samples are required for their discovery.
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff CF24 4HQ, UK.
authors.forename: Elliott
authors.initials: E
authors.lastname: Rees
authors.forename: James T R
authors.initials: JT
authors.lastname: Walters
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Chambert
authors.forename: Colm
authors.initials: C
authors.lastname: O'Dushlaine
authors.forename: Jin
authors.initials: J
authors.lastname: Szatkiewicz
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Richards
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Georgieva
authors.forename: Gerwyn
authors.initials: G
authors.lastname: Mahoney-Davies
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Legge
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Moran
authors.forename: Giulio
authors.initials: G
authors.lastname: Genovese
authors.forename: Douglas
authors.initials: D
authors.lastname: Levinson
authors.forename: Derek W
authors.initials: DW
authors.lastname: Morris
authors.forename: Paul
authors.initials: P
authors.lastname: Cormican
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.forename: Francis A
authors.initials: FA
authors.lastname: O'Neill
authors.forename: Brien
authors.initials: B
authors.lastname: Riley
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Aiden
authors.initials: A
authors.lastname: Corvin
authors.forename: Pamela
authors.initials: P
authors.lastname: Sklar
authors.forename: Christina
authors.initials: C
authors.lastname: Hultman
authors.forename: Carlos
authors.initials: C
authors.lastname: Pato
authors.forename: Michele
authors.initials: M
authors.lastname: Pato
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Sullivan
authors.forename: Pablo V
authors.initials: PV
authors.lastname: Gejman
authors.forename: Steven A
authors.initials: SA
authors.lastname: McCarroll
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: George
authors.initials: G
authors.lastname: Kirov
mesh_terms: D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D002885:Chromosomes, Human, Pair 16; D003598:Cytoskeletal Proteins / Q000235:genetics*; D056915:DNA Copy Number Variations; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D020440:Gene Duplication; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000235:genetics*
chemical_list: C533277:CGNL1 protein, human; D003598:Cytoskeletal Proteins; D050580:Excitatory Amino Acid Transporter 3; C493400:SLC1A1 protein, human