title: Association analyses between brain-expressed fatty-acid binding protein (FABP) genes and schizophrenia and bipolar disorder.
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.
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors: Yoshimi
authors: Y
authors: Iwayama
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors: Eiji
authors: E
authors: Hattori
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors: Motoko
authors: M
authors: Maekawa
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors: Kazuo
authors: K
authors: Yamada
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors: Tomoko
authors: T
authors: Toyota
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors: Tetsuo
authors: T
authors: Ohnishi
authors: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors: Yasuhide
authors: Y
authors: Iwata
authors: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors: Kenji J
authors: KJ
authors: Tsuchiya
authors: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors: Genichi
authors: G
authors: Sugihara
authors: Department of Psychiatry and Neurobiology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan.
authors: Mitsuru
authors: M
authors: Kikuchi
authors: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors: Kenji
authors: K
authors: Hashimoto
authors: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
authors: Masaomi
authors: M
authors: Iyo
authors: Seiwa Hospital, Institute of Neuropsychiatry, Tokyo, Japan.
authors: Toshiya
authors: T
authors: Inada
authors: Department of Mental Disorder Research, National Institute of Neuroscience, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Kunugi
authors: Department of Psychiatry, Graduate School of Medicine, Nagoya University, Aichi, Japan.
authors: Norio
authors: N
authors: Ozaki
authors: Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan.
authors: Nakao
authors: N
authors: Iwata
authors: Department of Psychiatry and Genome Research Center, Teikyo University of Medicine, Tokyo, Japan.
authors: Shinichiro
authors: S
authors: Nanko
authors: Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan.
authors: Kazuya
authors: K
authors: Iwamoto
authors: Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan.
authors: Yuji
authors: Y
authors: Okazaki
authors: Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan.
authors: Tadafumi
authors: T
authors: Kato
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.|CREST, Japanese Science and Technology Agency, Tokyo, Japan.
authors: Takeo
authors: T
authors: Yoshikawa
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D000074026:Fatty Acid Binding Protein 3; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins / Q000235:genetics*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C493408:FABP3 protein, human; C493412:FABP5 protein, human; C107608:FABP7 protein, human; D000074026:Fatty Acid Binding Protein 3; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005231:Fatty Acids, Unsaturated; D025521:Tumor Suppressor Proteins