Genome-wide burden of deleterious coding variants increased in schizophrenia

• Published in: Nature communications Vol. 6; no. 1; p. 7501
• Main Authors: Loohuis, Loes M. Olde, Vorstman, Jacob A. S., Ori, Anil P., Staats, Kim A., Wang, Tina, Richards, Alexander L., Leonenko, Ganna, Walters, James T., DeYoung, Joseph, Cantor, Rita M., Ophoff, Roel A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.07.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 631/208/205/2138; 631/208/457/649/2219; 692/420/2489/144; 692/699/476/1799; Alleles; Case-Control Studies; Cases (containers); Codon, Terminator - genetics; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Genomes; Genotype; Humanities and Social Sciences; Humans; Male; Mental disorders; multidisciplinary; Multifactorial Inheritance; Mutation; Neural coding; Polygenic inheritance; Polymorphism, Single Nucleotide; Population genetics; RNA Splice Sites - genetics; Schizophrenia; Schizophrenia - genetics; Science; Science (multidisciplinary); Whites - genetics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms8501

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. Schizophrenia is a complex disorder with high heritability but poorly understood genetics. Here Olde Loohuis et al. compare schizophrenia patients to unaffected individuals and identify an increased individual burden of rare deleterious mutations in patients.