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

Artikel i vetenskaplig tidskrift
Författare O. Pain
F. Dudbridge
A. G. Cardno
D. Freeman
Y. Lu
Sebastian Lundström
P. Lichtenstein
A. Ronald
Publicerad i American Journal of Medical Genetics Part B-Neuropsychiatric Genetics
Volym 177
Nummer/häfte 4
Sidor 416-425
ISSN 1552-4841
Publiceringsår 2018
Publicerad vid Gillbergcentrum
Centrum för etik, juridik och mental hälsa
Sidor 416-425
Språk en
Länkar https://doi.org/10.1002/ajmg.b.3263...
Ämnesord adolescence, ALSPAC, GWAS, psychotic-like experiences, schizophrenia, population-based cohort, general-population, young adulthood, depressive, symptoms, birth-cohort, association, schizophrenia, childhood, twin, risk, Genetics & Heredity, Psychiatry
Ämneskategorier Psykiatri, Medicinsk genetik

Sammanfattning

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.

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