title: Influence of the NRGN gene on intellectual ability in schizophrenia.
abstract: Genome-wide association studies have reported an association between schizophrenia and rs12807809 of the neurogranin (NRGN) gene. We have recently found that an rs12807809-rs12278912 haplotype of the gene is associated with schizophrenia in a Japanese population and that the NRGN expression of the high-risk TG haplotype is lower than that of the protective TA haplotype in immortalized lymphoblasts. In this study, we investigated the influences of neurogranin genotypes (rs12807809 and rs12278912), haplotypes and diplotypes and genetic variant-diagnosis interactions on intellectual ability in 414 Japanese patients with schizophrenia and healthy subjects. We detected possible effects of the genome-wide screen-supported rs12807809, haplotypes, diplotypes and their genetic variant-diagnosis interactions on intellectual abilities at the threshold level of P<0.05. After applying Bonferroni correction for 13 genotype measures and setting P-values for significance (P<0.0039; 0.05/13), three effects remained significant: the rs12807809-rs12278912 diplotype-diagnosis interactions on performance intelligence quotient (CG/CG: P=3.9 × 10(-13); TA/TA: P=1.1 × 10(-7)) and TA/TA diplotype on performance intelligence quotient in patients with schizophrenia (P=8.2 × 10(-8)) remained significant. The intellectual abilities of the high-risk TG/TG diplotype of the neurogranin gene were lower compared to those with the non-risk TA/TA diplotype. Our findings suggest that the genetic risk variant in the neurogranin gene may be related to reduced intellectual ability.
authors.affiliation: 1] Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan [2] Core Research for Evolutionary Science and Technology (CREST) of Japan Science and Technology Agency (JST), Saitama, Japan [3] National Hospital Organization, Yamato Mental-Medical Center, Nara, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ohi
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Fukumoto
authors.forename: Hidenaga
authors.initials: H
authors.lastname: Yamamori
authors.forename: Satomi
authors.initials: S
authors.lastname: Umeda-Yano
authors.forename: Michiko
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Masao
authors.initials: M
authors.lastname: Iwase
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kazui
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006239:Haplotypes; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007360:Intelligence / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D051579:Neurogranin / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult
chemical_list: C496649:NRGN protein, human; D051579:Neurogranin