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Exome arrays capture polygenic rare variant contributions to schizophrenia.
Richards, A L; Leonenko, G; Walters, J T; Kavanagh, D H; Rees, E G; Evans, A; Chambert, K D; Moran, J L; Goldstein, J; Neale, B M; McCarroll, S A; Pocklington, A J; Holmans, P A; Owen, M J; O'Donovan, M C.
Afiliación
  • Richards AL; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Cardiff CF24 4HQ, UK.
  • Leonenko G; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Cardiff CF24 4HQ, UK.
  • Walters JT; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Cardiff CF24 4HQ, UK.
  • Kavanagh DH; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Cardiff CF24 4HQ, UK, Icahn School of Medicine at Mount Sinai, 1468 Madison Ave, New York, NY 10029, USA.
  • Rees EG; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Cardiff CF24 4HQ, UK.
  • Evans A; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Cardiff CF24 4HQ, UK.
  • Chambert KD; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA and.
  • Moran JL; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA and.
  • Goldstein J; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA and.
  • Neale BM; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA and Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • McCarroll SA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA and.
  • Pocklington AJ; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Cardiff CF24 4HQ, UK.
  • Holmans PA; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Cardiff CF24 4HQ, UK.
  • Owen MJ; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Cardiff CF24 4HQ, UK.
  • O'Donovan MC; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Cardiff CF24 4HQ, UK, odonovanmc@cardiff.ac.uk.
Hum Mol Genet ; 25(5): 1001-7, 2016 Mar 01.
Article en En | MEDLINE | ID: mdl-26740555
Schizophrenia is a highly heritable disorder. Genome-wide association studies based largely on common alleles have identified over 100 schizophrenia risk loci, but it is also evident from studies of copy number variants (CNVs) and from exome-sequencing studies that rare alleles are also involved. Full characterization of the contribution of rare alleles to the disorder awaits the deployment of sequencing technology in very large sample sizes, meanwhile, as an interim measure, exome arrays allow rare non-synonymous variants to be sampled at a fraction of the cost. In an analysis of exome array data from 13 688 individuals (5585 cases and 8103 controls) from the UK, we found that rare (minor allele frequency < 0.1%) variant association signal was enriched among genes that map to autosomal loci that are genome-wide significant (GWS) in common variant studies of schizophrenia genome-wide association study (PGWAS = 0.01) as well as gene sets known to be enriched for rare variants in sequencing studies (PRARE = 0.026). We also identified the gene-wise equivalent of GWS support for WDR88 (WD repeat-containing protein 88), a gene of unknown function (P = 6.5 × 10(-7)). Rare alleles represented on exome chip arrays contribute to the genetic architecture of schizophrenia, but as is the case for GWAS, very large studies are required to reveal additional susceptibility alleles for the disorder.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esquizofrenia / Proteínas / Carácter Cuantitativo Heredable / Predisposición Genética a la Enfermedad / Sitios de Carácter Cuantitativo / Alelos / Proteínas del Tejido Nervioso Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esquizofrenia / Proteínas / Carácter Cuantitativo Heredable / Predisposición Genética a la Enfermedad / Sitios de Carácter Cuantitativo / Alelos / Proteínas del Tejido Nervioso Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido