title: Association of the neuronal cell adhesion molecule (NRCAM) gene variants with autism.
abstract: Autism is a severe neurodevelopmental disorder of early childhood. Genetic factors play an important role in the aetiology of the disorder. In this study, we considered the NRCAM gene as a candidate gene of autism. This gene is expressed in the central nervous system and located in the 7q region, a susceptibility locus of autism. We conducted a case-control study of 18 single nucleotide polymorphisms (SNPs) within the NRCAM gene for possible association with autism in 170 autistic patients and 214 normal controls in a Japanese population. Seven SNPs in the NRCAM gene were significantly associated with autism, among which rs2300045 indicated the most prominent result (p=0.0009 uncorrected, p=0.017 corrected). In haplotype analyses, several individual haplotypes, including a common NRCAM haplotype C-T-T-C-T-T-G-C for rs3763463, rs1859767, rs1034825, rs2300045, rs2300043, rs2300039, rs722519, and rs2216259, showed a significant association after Bonferroni correction (p=0.0035 uncorrected, p=0.028 corrected). These haplotypes were located in the 5' intron-2 region of the gene. In addition, we also assessed the above mentioned SNPs and haplotypes using the transmission disequilibrium test with 148 trios of autistic families. Haplotype G-T-T-T-T-C-G-C in the same eight SNPs was also associated with autism. In summary, our findings provide evidence for a significant association of NRCAM with autism. Considering the important role of the NRCAM gene in brain development, our results therefore indicated that the NRCAM gene is one of the strong candidate genes for autism.
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. PXX03135@nifty.ne.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Marui
authors.forename: Ikuko
authors.initials: I
authors.lastname: Funatogawa
authors.forename: Shinko
authors.initials: S
authors.lastname: Koishi
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Ohiko
authors.initials: O
authors.lastname: Hashimoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Nanba
authors.forename: Hisami
authors.initials: H
authors.lastname: Nishida
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kasai
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kano
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sasaki
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Kato
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001321:Autistic Disorder / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003627:Data Interpretation, Statistical; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D055815:Young Adult
chemical_list: D015815:Cell Adhesion Molecules; C491152:NRCAM protein, human