title: Common variants at 1p36 are associated with superior frontal gyrus volume.
abstract: The superior frontal gyrus (SFG), an area of the brain frequently found to have reduced gray matter in patients with schizophrenia, is involved in self-awareness and emotion, which are impaired in schizophrenia. However, no genome-wide association studies of SFG volume have investigated in patients with schizophrenia. To identify single-nucleotide polymorphisms (SNPs) associated with SFG volumes, we demonstrated a genome-wide association study (GWAS) of gray matter volumes in the right or left SFG of 158 patients with schizophrenia and 378 healthy subjects. We attempted to bioinformatically ascertain the potential effects of the top hit polymorphism on the expression levels of genes at the genome-wide region. We found associations between five variants on 1p36.12 and the right SFG volume at a widely used benchmark for genome-wide significance (P<5.0 × 10(-8)). The strongest association was observed at rs4654899, an intronic SNP in the eukaryotic translation initiation factor 4 gamma, 3 (EIF4G3) gene on 1p36.12 (P=7.5 × 10(-9)). No SNP with genome-wide significance was found in the volume of the left SFG (P>5.0 × 10(-8)); however, the rs4654899 polymorphism was identified as the locus with the second strongest association with the volume of the left SFG (P=1.5 × 10(-6)). In silico analyses revealed a proxy SNP of rs4654899 had effect on gene expression of two genes, HP1BP3 lying 3' to EIF4G3 (P=7.8 × 10(-6)) and CAPN14 at 2p (P=6.3 × 10(-6)), which are expressed in moderate-to-high levels throughout the adult human SFG. These results contribute to understand genetic architecture of a brain structure possibly linked to the pathophysiology of schizophrenia.
authors.affiliation: 1] Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan [2] Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Yahaba, Iwate, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Yamashita
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohi
authors.affiliation: 1] Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan [2] Department of Molecular Neuropsychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamamori
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yasuda
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Biofunctional Imaging, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fukunaga
authors.affiliation: Department of Neuropsychiatry, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nemoto
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tochigi
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Onitsuka
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamasue
authors.affiliation: Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iidaka
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Iwata
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: 1] Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan [2] Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kasai
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Ozaki
mesh_terms: D000328:Adult; D001931:Brain Mapping / Q000379:methods; D019295:Computational Biology / Q000379:methods; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D015870:Gene Expression / Q000235:genetics; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*