An association screen of myelin-related genes implicates the chromosome 22q11 PIK4CA gene in schizophrenia.

TitleAn association screen of myelin-related genes implicates the chromosome 22q11 PIK4CA gene in schizophrenia.
Publication TypeJournal Article
Year of Publication2008
AuthorsJungerius, BJ, Hoogendoorn MLC, Bakker SC, Van't Slot R, Bardoel AF, Ophoff RA, Wijmenga C, Kahn RS, Sinke RJ
JournalMolecular psychiatry
Volume13
Issue11
Pagination1060-8
Date Published2008 Nov
ISSN1476-5578
KeywordsChi-Square Distribution, Chromosomes, Human, Pair 22, Cohort Studies, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Linkage Disequilibrium, Male, Myelin Proteins, Phosphotransferases (Alcohol Group Acceptor), Polymorphism, Single Nucleotide, Schizophrenia
Abstract

Several lines of evidence, including expression analyses, brain imaging and genetic studies suggest that the integrity of myelin is disturbed in schizophrenia patients. In this study, we first reconstructed a pathway of 138 myelin-related genes, all involved in myelin structure, composition, development or maintenance. Then we performed a two-stage association analysis on these 138 genes using 771 single nucleotide polymorphisms (SNPs). Analysis of our data from 310 cases vs 880 controls demonstrated association of 10 SNPs from six genes. Specifically, we observed highly significant P-values for association in PIK4CA (observed P=6.1 x 10(-6)). These findings remained significant after Bonferroni correction for 771 tests. The PIK4CA gene is located in the chromosome 22q11 deletion syndrome region, which is of particular interest because it has been implicated in schizophrenia. We also report weak association of SNPs in PIK3C2G, FGF1, FGFR1, ARHGEF10 and PSAP (observed P

DOI10.1038/ng.2250
Alternate JournalMol. Psychiatry