Association analyses between brain-expressed fatty-acid binding protein (FABP) genes and schizophrenia and bipolar disorder

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 aci...

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Published in:American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2010-03, Vol.153B (2), p.484-493
Main Authors: 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
Format: Article
Language:English
Subjects:
Adult
Adult and adolescent clinical studies
Biological and medical sciences
Bipolar Disorder - genetics
Bipolar disorders
Carrier Proteins - genetics
Case-Control Studies
copy number polymorphism
FABP3
FABP5
FABP7
Fatty Acid Binding Protein 3
Fatty Acid-Binding Protein 7
Fatty Acid-Binding Proteins - genetics
Fatty Acids, Unsaturated - metabolism
Female
Genetics
Haplotypes
Humans
Male
Medical genetics
Medical sciences
Middle Aged
Miscellaneous
Mood disorders
Polymorphism, Genetic
Polymorphism, Single Nucleotide
polyunsaturated fatty acid
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychoses
Schizophrenia
Schizophrenia - genetics
Tumor Suppressor Proteins - genetics
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Summary: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. © 2009 Wiley‐Liss, Inc.
ISSN:1552-4841
1552-485X
DOI:10.1002/ajmg.b.31004