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 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.

SUBMITTER: Stokowy T 

PROVIDER: S-EPMC5931982 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature