Genetic variation of UBE3A is associated with schizotypy in a population of typical individuals

Psychiatry Res. 2019 May:275:94-99. doi: 10.1016/j.psychres.2019.03.019. Epub 2019 Mar 14.

Abstract

The maternally expressed imprinted gene UBE3A has been implicated in autism, schizophrenia and psychosis. The phenotype of Angelman syndrome, caused by loss of UBE3A expression, involves autism spectrum traits, while Prader-Willi syndrome, where the genotype of maternal disomy increases dosage of UBE3A, shows high penetrance for the development of psychosis. Maternal duplications of the 15q11-q13 chromosome region that overlap the imprinted region also show an association with schizophrenia, further implying a connection between increased dosage of UBE3A and the development of schizophrenia and psychosis. We phenotyped a large population of typical individuals for autism spectrum and schizotypal traits and genotyped them for a set of SNPs in UBE3A. Genetic variation of rs732739, an intronic SNP tagging a large haplotype spanning nearly the entire range of UBE3A, was significantly associated with variation in total schizotypy. Our results provide an independent line of evidence, connecting the imprinted UBE3A gene to the schizophrenia spectrum.

Keywords: 15q11-q13 duplication; Angelman syndrome; Autism spectrum disorder; Genomic imprinting; Prader-Willi syndrome; Schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angelman Syndrome / genetics
  • Autistic Disorder / genetics
  • Chromosomes, Human, Pair 15 / genetics
  • Female
  • Gene Dosage
  • Genomic Imprinting*
  • Genotype
  • Humans
  • Male
  • Maternal Inheritance*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Prader-Willi Syndrome / genetics
  • Psychotic Disorders / genetics*
  • Schizotypal Personality Disorder / genetics*
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • UBE3A protein, human
  • Ubiquitin-Protein Ligases