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

• Main Authors: 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
• Format: Article
• Language: English
• Published: Nature Publishing Group 2018-05-01
• Series: Scientific Reports
• Online Access: https://doi.org/10.1038/s41598-018-25280-4

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.