Psychotic experiences (PEs) are traits in the general population that at the extreme characterize the symptoms of disorders such as schizophrenia. It is common to have PEs during adolescence and they predict later psychiatric disorders (McGrath et al, 2016, Am J Psych). At the same time, the majority of PEs dissipate over time. Twin studies show that approximately 30-50% of the variance in PEs in mid-adolescence is explained by twin heritability (Zavos et al, 2014, JAMA Psychiatry). This study aimed to identify novel genetic variants associated with specific PE domains in adolescence, and to test for overlap in genetic influences between PEs as traits in adolescence and schizophrenia, bipolar disorder, and major depression in adults.
The full spectra of PEs, both in terms of severity and type (positive, cognitive, and negative), were assessed using self- and parent-ratings of quantitative traits in three European community samples aged 15-19 years (Final N including siblings = 6297-10098). A mega-genome-wide association study (mega-GWAS) was conducted on normalized scales with imputed data on a common reference panel across all samples. Several approaches (LD score regression, and polygenic risk score [PRS] analysis and AVENGME) were applied to estimate the degree of genetic covariance between PEs in adolescence and clinically recognized psychiatric conditions (schizophrenia, bipolar disorder, and major depression).
Genomic-relatedness-based restricted maximum likelihood returned SNP-heritability estimates of 3-9%. In the largest GWAS on PEs to date, mega-analysis returned one genome-wide significant association with an imputed SNP. PRS analysis revealed that the Psychiatric Genomic Consortium 2 (PGC2) schizophrenia PRS significantly predicted all domains of adolescent PEs (Paranoia and Hallucinations only in non-zero scorers), explaining 0.1-0.2% of variance. The PGC2 major depression PRS significantly predicted Anhedonia and Parent-rated Negative Symptoms in adolescence, explaining 0.1-0.2% of variance. Other methods concurred in showing modest genetic covariance between specific PEs and psychiatric disorders.
Psychotic experiences in the community during adolescence show additive genetic effects and partly share genetic influences with psychiatric disorders, specifically schizophrenia and major depression.
