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Genome-wide burden of deleterious coding variants increased in schizophrenia

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 le...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499856/
https://www.ncbi.nlm.nih.gov/pubmed/26158538
http://dx.doi.org/10.1038/ncomms8501
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author 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.
author_facet 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.
author_sort Loohuis, Loes M. Olde
collection PubMed
description 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.
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spelling pubmed-44998562015-07-28 Genome-wide burden of deleterious coding variants increased in schizophrenia 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. Nat Commun Article 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. Nature Pub. Group 2015-07-09 /pmc/articles/PMC4499856/ /pubmed/26158538 http://dx.doi.org/10.1038/ncomms8501 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
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.
Genome-wide burden of deleterious coding variants increased in schizophrenia
title Genome-wide burden of deleterious coding variants increased in schizophrenia
title_full Genome-wide burden of deleterious coding variants increased in schizophrenia
title_fullStr Genome-wide burden of deleterious coding variants increased in schizophrenia
title_full_unstemmed Genome-wide burden of deleterious coding variants increased in schizophrenia
title_short Genome-wide burden of deleterious coding variants increased in schizophrenia
title_sort genome-wide burden of deleterious coding variants increased in schizophrenia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499856/
https://www.ncbi.nlm.nih.gov/pubmed/26158538
http://dx.doi.org/10.1038/ncomms8501
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