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Association study of Nogo‐related genes with schizophrenia in a Japanese case–control sample
Author(s) -
Jitoku Daisuke,
Hattori Eiji,
Iwayama Yoshimi,
Yamada Kazuo,
Toyota Tomoko,
Kikuchi Mitsuru,
Maekawa Motoko,
Nishikawa Toru,
Yoshikawa Takeo
Publication year - 2011
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.31199
Subject(s) - single nucleotide polymorphism , linkage disequilibrium , genetics , genetic association , biology , genome wide association study , haplotype , snp , imputation (statistics) , allele , genotype , gene , machine learning , computer science , missing data
Many studies have suggested that myelin dysfunction may be causally involved in the pathogenesis of schizophrenia. Nogo (RTN4), myelin‐associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMG) all bind to the common receptor, Nogo‐66 receptor 1 (RTN4R). We examined 68 single nucleotide polymorphisms (SNPs) (51 with genotyping and 17 with imputation analysis) from these four genes for genetic association with schizophrenia, using a 2,120 case–control sample from the Japanese population. Allelic tests showed nominally significant association of two RTN4 SNPs ( P = 0.047 and 0.037 for rs11894868 and rs2968804, respectively) and two MAG SNPs ( P = 0.034 and 0.029 for rs7249617 and rs16970218, respectively) with schizophrenia. The MAG SNP rs7249617 also showed nominal significance in a genotypic test ( P = 0.017). In haplotype analysis, the MAG haplotype block including rs7249617 and rs16970218 showed nominal significance ( P = 0.008). These associations did not remain significant after correction for multiple testing, possibly due to their small genetic effect. In the imputation analysis of RTN4 , the untyped SNP rs2972090 showed nominally significant association ( P = 0.032) and several imputed SNPs showed marginal associations. Moreover, in silico analysis (PolyPhen) of a missense variant (rs11677099: Asp357Val), which is in strong linkage disequilibrium with rs11894868, predicted a deleterious effect on Nogo protein function. Despite a failure to detect robust associations in this Japanese cohort, our nominally positive signals, taken together with previously reported biological and genetic findings, add further support to the “disturbed myelin system theory of schizophrenia” across different populations. © 2011 Wiley‐Liss, Inc.