Association analyses between brain-expressed Fatty-Acid Binding Protein (FABP) genes and schizophrenia and bipolar disorder

Yoshimi Iwayama, Eiji Hattori, Motoko Maekawa, Kazuo Yamada, Tomoko Toyota, Tetsuo Ohnishi, Yasuhide Iwata, Kenji J. Tsuchiya, Genichi Sugihara, Mitsuru Kikuchi, Kenji Hashimoto, Masaomi Iyo, Toshiya Inada, Hiroshi Kunugi, Norio Ozaki, Nakao Iwata, Shinichiro Nanko, Kazuya Iwamoto, Yuji Okazaki, Tadafumi KatoTakeo Yoshikawa

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24 Citations (Scopus)

Abstract

Deficits in prepulse inhibition (PPI) are a biological marker for psychiatric illnesses such as schizophrenia and bipolar disorder. To unravel PPI-controlling mechanisms, we previously performed quantitative trait loci (QTL) analysis in mice, and identified Fabp7, that encodes a brain-type fatty acid binding protein (Fabp), as a causative gene. In that study, human FABP7 showed genetic association with schizophrenia. FABPs constitute a gene family, of which members FABP5 and FABP3 are also expressed in the brain. These FABP proteins are molecular chaperons for polyunsaturated fatty acids (PUFAs) such as arachidonic and docosahexaenoic acids. Additionally, the involvement of PUFAs has been documented in the pathophysiology of schizophrenia and mood disorders. Therefore in this study, we examined the genetic roles of FABP5 and 3 in schizophrenia (N=1,900 in combination with controls) and FABP7, 5, and 3 in bipolar disorder (N=1,762 in the case-control set). Three single nucleotide polymorphisms (SNPs) from FABP7 showed nominal association with bipolar disorder, and haplotypes of the same gene showed empirical associations with bipolar disorder even after correction of multiple testing. We could not perform association studies on FABP5, due to the lack of informative SNPs. FABP3 displayed no association with either disease. Each FABP is relatively small and it is assumed that there are multiple regulatory elements that control gene expression. Therefore, future identification of unknown regulatory elements will be necessary to make a more detailed analysis of their genetic contribution to mental illnesses.

Original languageEnglish
Pages (from-to)484-493
Number of pages10
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume153
Issue number2
DOIs
Publication statusPublished - 03-2010

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Iwayama, Y., Hattori, E., Maekawa, M., Yamada, K., Toyota, T., Ohnishi, T., Iwata, Y., Tsuchiya, K. J., Sugihara, G., Kikuchi, M., Hashimoto, K., Iyo, M., Inada, T., Kunugi, H., Ozaki, N., Iwata, N., Nanko, S., Iwamoto, K., Okazaki, Y., ... Yoshikawa, T. (2010). Association analyses between brain-expressed Fatty-Acid Binding Protein (FABP) genes and schizophrenia and bipolar disorder. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 153(2), 484-493. https://doi.org/10.1002/ajmg.b.31004