The International Journal of Neuropsychopharmacology

Cambridge Journals Online - CUP Full-Text Page
The International Journal of Neuropsychopharmacology (2009), 12:1-10 Cambridge University Press
Copyright © 2008 CINP

Research Article

Association of the neuronal cell adhesion molecule (NRCAM) gene variants with autism

Tetsuya Maruia1a2 c1, Ikuko Funatogawaa3, Shinko Koishia4, Kenji Yamamotoa5, Hideo Matsumotoa6, Ohiko Hashimotoa7, Eiji Nanbaa8, Hisami Nishidaa9, Toshiro Sugiyamaa4, Kiyoto Kasaia1, Keiichiro Watanabea10, Yukiko Kanoa10 and Nobumasa Katoa1

a1 Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
a2 Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan
a3 Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan
a4 Aichi Children's Health and Medical Center, Obu, Japan
a5 Department of Psychiatry, Kitasato University School of Medicine, Sagamihara, Japan
a6 Department of Psychiatry, Tokai University School of Medicine, Isehara, Japan
a7 Department of Occupational Therapy, Faculty of Nursing and Rehabilitation, Aino University, Ibaraki, Japan
a8 Gene Research Center, Tottori University, Yonago, Japan
a9 Asunaro Hospital for Child and Adolescent Psychiatry, Tsu, Japan
a10 Department of Child Psychiatry, School of Medicine, University of Tokyo, Tokyo, Japan
Article author query
marui t [PubMed]  [Google Scholar]
funatogawa i [PubMed]  [Google Scholar]
koishi s [PubMed]  [Google Scholar]
yamamoto k [PubMed]  [Google Scholar]
matsumoto h [PubMed]  [Google Scholar]
hashimoto o [PubMed]  [Google Scholar]
nanba e [PubMed]  [Google Scholar]
nishida h [PubMed]  [Google Scholar]
sugiyama t [PubMed]  [Google Scholar]
kasai k [PubMed]  [Google Scholar]
watanabe k [PubMed]  [Google Scholar]
kano y [PubMed]  [Google Scholar]
kato n [PubMed]  [Google Scholar]


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.

(Received October 24 2007)

(Reviewed January 07 2008)

(Revised June 07 2008)

(Accepted June 13 2008)

(Online publication July 30 2008)

Key Words:Association study; autistic disorder; haplotype block; NRCAM gene


c1 Address for correspondence: T. Marui, M.D., Ph.D., Department of Neuropsychiatry, School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan. Tel.: +81-3-5800-9263 Fax: +81-42-379-4544 E-mail: