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

TY - JOUR

T1 - Genome-wide analysis of adolescent psychotic-like experiences shows genetic overlap with psychiatric disorders

AU - Pain, Oliver

AU - Dudbridge, Frank

AU - Cardno, Alastair G

AU - Freeman, Daniel

AU - Lu, Yi

AU - Lundstrom, Sebastian

AU - Lichtenstein, Paul

AU - Ronald, Angelica

N1 - © 2018 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

PY - 2018/6

Y1 - 2018/6

N2 - 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.

AB - 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.

KW - Adolescent

KW - Anhedonia

KW - Bipolar Disorder/genetics

KW - Depressive Disorder, Major/genetics

KW - European Continental Ancestry Group/genetics

KW - Female

KW - Genetic Predisposition to Disease/genetics

KW - Genetic Testing/methods

KW - Genome-Wide Association Study

KW - Hallucinations/psychology

KW - Humans

KW - Linkage Disequilibrium/genetics

KW - Male

KW - Multifactorial Inheritance/genetics

KW - Paranoid Disorders

KW - Polymorphism, Single Nucleotide/genetics

KW - Psychotic Disorders/genetics

KW - Risk Factors

KW - Schizophrenia/genetics

KW - Young Adult

U2 - 10.1002/ajmg.b.32630

DO - 10.1002/ajmg.b.32630

M3 - Article

C2 - 29603866

SN - 1552-4841

VL - 177

SP - 416

EP - 425

JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

IS - 4

ER -