title: Investigation of Rare Single-Nucleotide PCDH15 Variants in Schizophrenia and Autism Spectrum Disorders.
abstract: Both schizophrenia (SCZ) and autism spectrum disorders (ASD) are neuropsychiatric disorders with overlapping genetic etiology. Protocadherin 15 (PCDH15), which encodes a member of the cadherin super family that contributes to neural development and function, has been cited as a risk gene for neuropsychiatric disorders. Recently, rare variants of large effect have been paid attention to understand the etiopathology of these complex disorders. Thus, we evaluated the impacts of rare, single-nucleotide variants (SNVs) in PCDH15 on SCZ or ASD. First, we conducted coding exon-targeted resequencing of PCDH15 with next-generation sequencing technology in 562 Japanese patients (370 SCZ and 192 ASD) and detected 16 heterozygous SNVs. We then performed association analyses on 2,096 cases (1,714 SCZ and 382 ASD) and 1,917 controls with six novel variants of these 16 SNVs. Of these six variants, four (p.R219K, p.T281A, p.D642N, c.3010-1G>C) were ultra-rare variants (minor allele frequency < 0.0005) that may increase disease susceptibility. Finally, no statistically significant association between any of these rare, heterozygous PCDH15 point variants and SCZ or ASD was found. Our results suggest that a larger sample size of resequencing subjects is necessary to detect associations between rare PCDH15 variants and neuropsychiatric disorders.
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Ishizuka
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Chenyao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Jingrui
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Kushima
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Arioka
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Oya-Ito
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Yota
authors.initials: Y
authors.lastname: Uno
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mori
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Branko
authors.identifier: http://orcid.org/0000-0001-8982-4580
authors.initials: B
authors.lastname: Aleksic
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005091:Exons; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C498835:CDHR15, human; D000070585:Cadherin Related Proteins; D015820:Cadherins