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

journal contribution
posted on 30.04.2018, 14:01 by Oliver Pain, Frank Dudbridge, Alastair G. Cardno, Daniel Freeman, Yi Lu, Sebastian Lundstrom, Paul Lichtenstein, Angelica Ronald
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.


Medical Research Council, Grant/Award Numbers: G1100559 and MR/M021475/1; Medical Research Council and Wellcome, Grant/Award Number: 102215/2/13/2; Bloomsbury PhD studentship; NIHR Research Professorship; University of Bristol; Swedish Foundation for International Cooperation in Research and Higher Education (STINT); Swedish Council for Health, Working Life and Welfare; The Söderström‐Königska Foundation; Swedish Research Council (Medicine and SIMSAM)



American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2018

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American Journal of Medical Genetics Part B: Neuropsychiatric Genetics


Wiley for International Society of Psychiatric Genetics





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