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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7c6a8c2756cb4a62ab7238d70740552a
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spelling	oai:doaj.org-article:7c6a8c2756cb4a62ab7238d70740552a2021-12-02T16:08:02ZGenetic variation in 117 myelination-related genes in schizophrenia: Replication of association to lipid biosynthesis genes10.1038/s41598-018-25280-42045-2322https://doaj.org/article/7c6a8c2756cb4a62ab7238d70740552a2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25280-4https://doaj.org/toc/2045-2322Abstract 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.Tomasz StokowyTatiana PolushinaIda E. SønderbyRobert KarlssonSudheer GiddaluruStephanie Le HellardSarah E. BergenPatrick F. SullivanOle A. AndreassenSrdjan DjurovicChristina M. HultmanVidar M. SteenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
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 Portfolio
publishDate	2018
url	https://doaj.org/article/7c6a8c2756cb4a62ab7238d70740552a
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Genetic variation in 117 myelination-related genes in schizophrenia: Replication of association to lipid biosynthesis genes

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