Genome-wide analysis of adolescent psychotic-like experiences shows genetic overlap with psychiatric disorders

Oliver Pain, Frank Dudbridge, Alastair G Cardno, Daniel Freeman, Yi Lu, Sebastian Lundstrom, Paul Lichtenstein, Angelica Ronald

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)
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Abstract

This study aimed to test for overlap in genetic influences between psychotic-like experience traits shown by adolescents in the community, and clinically-recognized psychiatric disorders in adulthood, specifically schizophrenia, bipolar disorder, and major depression. The full spectra of psychotic-like experience domains, both in terms of their severity and type (positive, cognitive, and negative), were assessed using self- and parent-ratings in three European community samples aged 15-19 years (Final N incl. siblings = 6,297-10,098). A mega-genome-wide association study (mega-GWAS) for each psychotic-like experience domain was performed. Single nucleotide polymorphism (SNP)-heritability of each psychotic-like experience domain was estimated using genomic-relatedness-based restricted maximum-likelihood (GREML) and linkage disequilibrium- (LD-) score regression. Genetic overlap between specific psychotic-like experience domains and schizophrenia, bipolar disorder, and major depression was assessed using polygenic risk score (PRS) and LD-score regression. GREML returned SNP-heritability estimates of 3-9% for psychotic-like experience trait domains, with higher estimates for less skewed traits (Anhedonia, Cognitive Disorganization) than for more skewed traits (Paranoia and Hallucinations, Parent-rated Negative Symptoms). Mega-GWAS analysis identified one genome-wide significant association for Anhedonia within IDO2 but which did not replicate in an independent sample. PRS analysis revealed that the schizophrenia PRS significantly predicted all adolescent psychotic-like experience trait domains (Paranoia and Hallucinations only in non-zero scorers). The major depression PRS significantly predicted Anhedonia and Parent-rated Negative Symptoms in adolescence. Psychotic-like experiences during adolescence in the community show additive genetic effects and partly share genetic influences with clinically-recognized psychiatric disorders, specifically schizophrenia and major depression.

Original languageEnglish
Pages (from-to)416-425
Number of pages10
JournalAmerican Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Volume177
Issue number4
Early online date31 Mar 2018
DOIs
Publication statusPublished - Jun 2018

Keywords

  • Adolescent
  • Anhedonia
  • Bipolar Disorder/genetics
  • Depressive Disorder, Major/genetics
  • European Continental Ancestry Group/genetics
  • Female
  • Genetic Predisposition to Disease/genetics
  • Genetic Testing/methods
  • Genome-Wide Association Study
  • Hallucinations/psychology
  • Humans
  • Linkage Disequilibrium/genetics
  • Male
  • Multifactorial Inheritance/genetics
  • Paranoid Disorders
  • Polymorphism, Single Nucleotide/genetics
  • Psychotic Disorders/genetics
  • Risk Factors
  • Schizophrenia/genetics
  • Young Adult

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