title: Rare variants in the neurotrophin signaling pathway implicated in schizophrenia risk.
abstract: Multiple lines of evidence corroborate impaired signaling pathways as relevant to the underpinnings of schizophrenia. There has been an interest in neurotrophins, since they are crucial mediators of neurodevelopment and in synaptic connectivity in the adult brain. Neurotrophins and their receptors demonstrate aberrant expression patterns in cortical areas for schizophrenia cases in comparison to control subjects. There is little known about the contribution of neurotrophin genes in psychiatric disorders. To begin to address this issue, we conducted high-coverage targeted exome capture in a subset of neurotrophin genes in 48 comprehensively characterized cases with schizophrenia-related psychosis. We herein report rare missense polymorphisms and novel missense mutations in neurotrophin receptor signaling pathway genes. Furthermore, we observed that several genes have a higher propensity to harbor missense coding variants than others. Based on this initial analysis we suggest that rare variants and missense mutations in neurotrophin genes might represent genetic contributions involved across psychiatric disorders.
authors.affiliation: Skirball Institute of Biomolecular Medicine, Departments of Cell Biology, Physiology & Neuroscience and Psychiatry, New York University, New York, NY 10016, USA. Electronic address: Thorsten.Kranz@nyumc.org.
authors.forename: Thorsten M
authors.initials: TM
authors.lastname: Kranz
authors.affiliation: New York State Psychiatric Institute, Division of Clinical Phenomenology, 1051 Riverside Drive, New York, NY 10032, USA; Columbia University, Department of Psychiatry, New York, NY 10032, USA.
authors.forename: Ray R
authors.initials: RR
authors.lastname: Goetz
authors.affiliation: Mental Illness, Research, Education, and Clinical Center (MIRECC), James J Peters VA Medical Center, Bronx, NY 10468, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Walsh-Messinger
authors.affiliation: Department of Psychiatry, Social and Psychiatric Initiatives, New York University, 1 Park Avenue, 8th Floor Room 222, New York, NY 10016, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Goetz
authors.affiliation: Department of Psychiatry, Social and Psychiatric Initiatives, New York University, 1 Park Avenue, 8th Floor Room 222, New York, NY 10016, USA; University at Buffalo, Department of Psychiatry, Buffalo, NY, 14215, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Antonius
authors.affiliation: Genome Technology Center, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Dolgalev
authors.affiliation: Genome Technology Center, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Heguy
authors.affiliation: Department of Surgery, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Seandel
authors.affiliation: Department of Psychiatry, Social and Psychiatric Initiatives, New York University, 1 Park Avenue, 8th Floor Room 222, New York, NY 10016, USA.
authors.forename: Dolores
authors.initials: D
authors.lastname: Malaspina
authors.affiliation: Skirball Institute of Biomolecular Medicine, Departments of Cell Biology, Physiology & Neuroscience and Psychiatry, New York University, New York, NY 10016, USA.
authors.forename: Moses V
authors.initials: MV
authors.lastname: Chao
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D003863:Depression / Q000209:etiology; D005260:Female; D006801:Humans; D007360:Intelligence / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics*; D055815:Young Adult
chemical_list: D009414:Nerve Growth Factors
keywords: ARMS; De novo; Exome sequencing; Kidins220; Neurotrophin; Rare variant; Schizophrenia; Sporadic