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Sci Rep. 2018 May 2;8(1):6915. doi: 10.1038/s41598-018-25280-4.

Genetic variation in 117 myelination-related genes in schizophrenia: Replication of association to lipid biosynthesis genes.

Author information

1
NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
2
Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
3
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
4
NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Medicine, University of Oslo, Oslo, Norway.
5
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
6
Center for Psychiatric Genomics, Department of Genetics, University of North Carolina, Carolina, USA.
7
NORMENT - KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
8
NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway. vidar.martin.steen@helse-bergen.no.
9
Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway. vidar.martin.steen@helse-bergen.no.

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.

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