Genetic variation in 117 myelination-related genes in schizophrenia: Replication of association to lipid biosynthesis genes
Abstract Schizophrenia is a serious psychotic disorder with high heritability. Several common genetic variants, rare copy number variants and ultra-rare gene-disrupting mutations have been linked to disease susceptibility, but there is still a large gap between the estimated and explained heritabili...
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doaj-7c6a8c2756cb4a62ab7238d70740552a2020-12-08T04:26:57ZengNature Publishing GroupScientific Reports2045-23222018-05-01811810.1038/s41598-018-25280-4Genetic variation in 117 myelination-related genes in schizophrenia: Replication of association to lipid biosynthesis genesTomasz Stokowy0Tatiana Polushina1Ida E. Sønderby2Robert Karlsson3Sudheer Giddaluru4Stephanie Le Hellard5Sarah E. Bergen6Patrick F. Sullivan7Ole A. Andreassen8Srdjan Djurovic9Christina M. Hultman10Vidar M. Steen11NORMENT – KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of BergenNORMENT – KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of BergenDepartment of Medical Genetics, Oslo University HospitalDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetNORMENT – KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of BergenNORMENT – KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of BergenDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetNORMENT – KG Jebsen Centre for Psychosis Research, Department of Clinical Medicine, University of OsloNORMENT – KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of BergenDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetNORMENT – KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of BergenAbstract Schizophrenia is a serious psychotic disorder with high heritability. Several common genetic variants, rare copy number variants and ultra-rare gene-disrupting mutations have been linked to disease susceptibility, but there is still a large gap between the estimated and explained heritability. Since several studies have indicated brain myelination abnormalities in schizophrenia, we aimed to examine whether variants in myelination-related genes could be associated with risk for schizophrenia. We established a set of 117 myelination genes by database searches and manual curation. We used a combination of GWAS (SCZ_N = 35,476; CTRL_N = 46,839), exome chip (SCZ_N = 269; CTRL_N = 336) and exome sequencing data (SCZ_N = 2,527; CTRL_N = 2,536) from schizophrenia cases and healthy controls to examine common and rare variants. We found that a subset of lipid-related genes was nominally associated with schizophrenia (p = 0.037), but this signal did not survive multiple testing correction (FWER = 0.16) and was mainly driven by the SREBF1 and SREBF2 genes that have already been linked to schizophrenia. Further analysis demonstrated that the lowest nominal p-values were p = 0.0018 for a single common variant (rs8539) and p = 0.012 for burden of rare variants (LRP1 gene), but none of them survived multiple testing correction. Our findings suggest that variation in myelination-related genes is not a major risk factor for schizophrenia.https://doi.org/10.1038/s41598-018-25280-4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tomasz Stokowy Tatiana Polushina Ida E. Sønderby Robert Karlsson Sudheer Giddaluru Stephanie Le Hellard Sarah E. Bergen Patrick F. Sullivan Ole A. Andreassen Srdjan Djurovic Christina M. Hultman Vidar M. Steen |
spellingShingle |
Tomasz Stokowy Tatiana Polushina Ida E. Sønderby Robert Karlsson Sudheer Giddaluru Stephanie Le Hellard Sarah E. Bergen Patrick F. Sullivan Ole A. Andreassen Srdjan Djurovic Christina M. Hultman Vidar M. Steen Genetic variation in 117 myelination-related genes in schizophrenia: Replication of association to lipid biosynthesis genes Scientific Reports |
author_facet |
Tomasz Stokowy Tatiana Polushina Ida E. Sønderby Robert Karlsson Sudheer Giddaluru Stephanie Le Hellard Sarah E. Bergen Patrick F. Sullivan Ole A. Andreassen Srdjan Djurovic Christina M. Hultman Vidar M. Steen |
author_sort |
Tomasz Stokowy |
title |
Genetic variation in 117 myelination-related genes in schizophrenia: Replication of association to lipid biosynthesis genes |
title_short |
Genetic variation in 117 myelination-related genes in schizophrenia: Replication of association to lipid biosynthesis genes |
title_full |
Genetic variation in 117 myelination-related genes in schizophrenia: Replication of association to lipid biosynthesis genes |
title_fullStr |
Genetic variation in 117 myelination-related genes in schizophrenia: Replication of association to lipid biosynthesis genes |
title_full_unstemmed |
Genetic variation in 117 myelination-related genes in schizophrenia: Replication of association to lipid biosynthesis genes |
title_sort |
genetic variation in 117 myelination-related genes in schizophrenia: replication of association to lipid biosynthesis genes |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2018-05-01 |
description |
Abstract Schizophrenia is a serious psychotic disorder with high heritability. Several common genetic variants, rare copy number variants and ultra-rare gene-disrupting mutations have been linked to disease susceptibility, but there is still a large gap between the estimated and explained heritability. Since several studies have indicated brain myelination abnormalities in schizophrenia, we aimed to examine whether variants in myelination-related genes could be associated with risk for schizophrenia. We established a set of 117 myelination genes by database searches and manual curation. We used a combination of GWAS (SCZ_N = 35,476; CTRL_N = 46,839), exome chip (SCZ_N = 269; CTRL_N = 336) and exome sequencing data (SCZ_N = 2,527; CTRL_N = 2,536) from schizophrenia cases and healthy controls to examine common and rare variants. We found that a subset of lipid-related genes was nominally associated with schizophrenia (p = 0.037), but this signal did not survive multiple testing correction (FWER = 0.16) and was mainly driven by the SREBF1 and SREBF2 genes that have already been linked to schizophrenia. Further analysis demonstrated that the lowest nominal p-values were p = 0.0018 for a single common variant (rs8539) and p = 0.012 for burden of rare variants (LRP1 gene), but none of them survived multiple testing correction. Our findings suggest that variation in myelination-related genes is not a major risk factor for schizophrenia. |
url |
https://doi.org/10.1038/s41598-018-25280-4 |
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