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

Research output: Contribution to journalArticle

22 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 - 01-03-2010

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Bipolar Disorder
Fatty Acid-Binding Proteins
Schizophrenia
Unsaturated Fatty Acids
Genes
Single Nucleotide Polymorphism
Biological Psychiatry
Arachidonic Acids
Molecular Chaperones
Quantitative Trait Loci
Mood Disorders
Haplotypes
Biomarkers
Gene Expression
Fatty Acid-Binding Protein 7
Brain
Proteins
Prepulse Inhibition

All Science Journal Classification (ASJC) codes

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

Cite this

Iwayama, Yoshimi ; Hattori, Eiji ; Maekawa, Motoko ; Yamada, Kazuo ; Toyota, Tomoko ; Ohnishi, Tetsuo ; Iwata, Yasuhide ; Tsuchiya, Kenji J. ; Sugihara, Genichi ; Kikuchi, Mitsuru ; Hashimoto, Kenji ; Iyo, Masaomi ; Inada, Toshiya ; Kunugi, Hiroshi ; Ozaki, Norio ; Iwata, Nakao ; Nanko, Shinichiro ; Iwamoto, Kazuya ; Okazaki, Yuji ; Kato, Tadafumi ; Yoshikawa, Takeo. / Association analyses between brain-expressed Fatty-Acid Binding Protein (FABP) genes and schizophrenia and bipolar disorder. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2010 ; Vol. 153, No. 2. pp. 484-493.
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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.",
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Iwayama, Y, Hattori, E, Maekawa, M, Yamada, K, Toyota, T, Ohnishi, T, Iwata, Y, Tsuchiya, KJ, Sugihara, G, Kikuchi, M, Hashimoto, K, Iyo, M, Inada, T, Kunugi, H, Ozaki, N, Iwata, N, Nanko, S, Iwamoto, K, Okazaki, Y, Kato, T & 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, vol. 153, no. 2, pp. 484-493. https://doi.org/10.1002/ajmg.b.31004

Association analyses between brain-expressed Fatty-Acid Binding Protein (FABP) genes and schizophrenia and bipolar disorder. / Iwayama, Yoshimi; Hattori, Eiji; Maekawa, Motoko; Yamada, Kazuo; Toyota, Tomoko; Ohnishi, Tetsuo; Iwata, Yasuhide; Tsuchiya, Kenji J.; Sugihara, Genichi; Kikuchi, Mitsuru; Hashimoto, Kenji; Iyo, Masaomi; Inada, Toshiya; Kunugi, Hiroshi; Ozaki, Norio; Iwata, Nakao; Nanko, Shinichiro; Iwamoto, Kazuya; Okazaki, Yuji; Kato, Tadafumi; Yoshikawa, Takeo.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 153, No. 2, 01.03.2010, p. 484-493.

Research output: Contribution to journalArticle

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T1 - Association analyses between brain-expressed Fatty-Acid Binding Protein (FABP) genes and schizophrenia and bipolar disorder

AU - Iwayama, Yoshimi

AU - Hattori, Eiji

AU - Maekawa, Motoko

AU - Yamada, Kazuo

AU - Toyota, Tomoko

AU - Ohnishi, Tetsuo

AU - Iwata, Yasuhide

AU - Tsuchiya, Kenji J.

AU - Sugihara, Genichi

AU - Kikuchi, Mitsuru

AU - Hashimoto, Kenji

AU - Iyo, Masaomi

AU - Inada, Toshiya

AU - Kunugi, Hiroshi

AU - Ozaki, Norio

AU - Iwata, Nakao

AU - Nanko, Shinichiro

AU - Iwamoto, Kazuya

AU - Okazaki, Yuji

AU - Kato, Tadafumi

AU - Yoshikawa, Takeo

PY - 2010/3/1

Y1 - 2010/3/1

N2 - 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.

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