title: Genome-wide burden of deleterious coding variants increased in schizophrenia.
abstract: Schizophrenia is a common complex disorder with polygenic inheritance. Here we show that by using an approach that compares the individual loads of rare variants in 1,042 schizophrenia cases and 961 controls, schizophrenia cases carry an increased burden of deleterious mutations. At a genome-wide level, our results implicate non-synonymous, splice site as well as stop-altering single-nucleotide variations occurring at minor allele frequency of ≥ 0.01% in the population. In an independent replication sample of 5,585 schizophrenia cases and 8,103 controls of European ancestry we confirm an enrichment in cases of the alleles identified in our study. In addition, the genes implicated by the increased burden of rare coding variants highlight the involvement of neurodevelopment in the aetiology of schizophrenia.
authors.affiliation: Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Loes M Olde
authors.initials: LMO
authors.lastname: Loohuis
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands.
authors.forename: Jacob A S
authors.initials: JAS
authors.lastname: Vorstman
authors.affiliation: Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Anil P
authors.initials: AP
authors.lastname: Ori
authors.affiliation: Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Staats
authors.affiliation: Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Wang
authors.affiliation: MRC Centre for Psychiatric Genetics and Genomics, Cardiff University, Cardiff CF24 4HQ, UK.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Richards
authors.affiliation: MRC Centre for Psychiatric Genetics and Genomics, Cardiff University, Cardiff CF24 4HQ, UK.
authors.forename: Ganna
authors.initials: G
authors.lastname: Leonenko
authors.affiliation: MRC Centre for Psychiatric Genetics and Genomics, Cardiff University, Cardiff CF24 4HQ, UK.
authors.forename: James T
authors.initials: JT
authors.lastname: Walters
authors.affiliation: Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: DeYoung
authors.affiliation: Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California 90095, USA.|Department of Human Genetics, University of California Los Angeles, Los Angeles 90095, USA.
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.affiliation: Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California 90095, USA.|Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands.|Department of Human Genetics, University of California Los Angeles, Los Angeles 90095, USA.
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D018388:Codon, Terminator / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide; D022821:RNA Splice Sites / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D018388:Codon, Terminator; D022821:RNA Splice Sites