title: Asymmetry within and around the human planum temporale is sexually dimorphic and influenced by genes involved in steroid hormone receptor activity.
abstract: The genetic determinants of cerebral asymmetries are unknown. Sex differences in asymmetry of the planum temporale (PT), that overlaps Wernicke's classical language area, have been inconsistently reported. Meta-analysis of previous studies has suggested that publication bias established this sex difference in the literature. Using probabilistic definitions of cortical regions we screened over the cerebral cortex for sexual dimorphisms of asymmetry in 2337 healthy subjects, and found the PT to show the strongest sex-linked asymmetry of all regions, which was supported by two further datasets, and also by analysis with the FreeSurfer package that performs automated parcellation of cerebral cortical regions. We performed a genome-wide association scan (GWAS) meta-analysis of PT asymmetry in a pooled sample of 3095 subjects, followed by a candidate-driven approach which measured a significant enrichment of association in genes of the 'steroid hormone receptor activity' and 'steroid metabolic process' pathways. Variants in the genes and pathways identified may affect the role of the PT in language cognition.
authors.affiliation: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands; International Max Planck Research School for Language Sciences, Nijmegen, The Netherlands.
authors.forename: Tulio
authors.initials: T
authors.lastname: Guadalupe
authors.affiliation: Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Marcel P
authors.initials: MP
authors.lastname: Zwiers
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Greifswald, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Wittfeld
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Teumer
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Alejandro Arias
authors.initials: AA
authors.lastname: Vasquez
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Martine
authors.initials: M
authors.lastname: Hoogman
authors.affiliation: Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands; Neurobiology of Language Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Hagoort
authors.affiliation: Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Guillen
authors.initials: G
authors.lastname: Fernandez
authors.affiliation: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Buitelaar
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: van Bokhoven
authors.affiliation: Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Hegenscheid
authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition & Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Simon E
authors.initials: SE
authors.lastname: Fisher
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Greifswald, Germany; Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Grabe
authors.affiliation: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition & Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands. Electronic address: clyde.francks@mpi.nl.
authors.forename: Clyde
authors.initials: C
authors.lastname: Francks
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D063405:Anatomic Variation / Q000235:genetics*; D002540:Cerebral Cortex / Q000033:anatomy & histology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D066128:Gray Matter / Q000033:anatomy & histology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011987:Receptors, Steroid / Q000235:genetics*; D012727:Sex Characteristics; D013702:Temporal Lobe / Q000033:anatomy & histology*; D065813:Wernicke Area / Q000033:anatomy & histology*; D055815:Young Adult
chemical_list: D047492:Peroxisome Proliferator-Activated Receptors; D011987:Receptors, Steroid; D003577:Cytochrome P-450 Enzyme System
keywords: Asymmetry; Genome-wide association scan; Planum temporale; Sexual dimorphism; Steroid hormones