Author:

Keywords:

Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, DE-NOVO MUTATIONS, ASSOCIATION, POPULATION, FREQUENCY, LOCI, Alleles, Case-Control Studies, Codon, Terminator, Female, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Male, Multifactorial Inheritance, Polymorphism, Single Nucleotide, RNA Splice Sites, Schizophrenia, White People, GROUP consortium

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.