Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood

Neurocognitive abilities constitute complex traits with considerable heritability. Impaired neurocognition is typically observed in schizophrenia (SZ), whereas convergent evidence has shown shared genetic determinants between neurocognition and SZ. Here, we report a genome‐wide association study (GW...

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Published in:American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2015-07, Vol.168B (5), p.392-401
Main Authors: Hatzimanolis, Alex, Bhatnagar, Pallav, Moes, Anna, Wang, Ruihua, Roussos, Panos, Bitsios, Panos, Stefanis, Costas N., Pulver, Ann E., Arking, Dan E., Smyrnis, Nikolaos, Stefanis, Nicholas C., Avramopoulos, Dimitrios
Format: Article
Language:English
Subjects:
Adolescent
cognition
Cognition Disorders - genetics
endophenotype
Female
Gene Expression Regulation
Genetic Predisposition to Disease
Genetics
Genome-Wide Association Study
Genotype
GWAS
Humans
Male
Memory, Short-Term - physiology
Polymorphism, Single Nucleotide - genetics
psychosis
Risk
Schizophrenia - genetics
working memory
Young Adult
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Summary:Neurocognitive abilities constitute complex traits with considerable heritability. Impaired neurocognition is typically observed in schizophrenia (SZ), whereas convergent evidence has shown shared genetic determinants between neurocognition and SZ. Here, we report a genome‐wide association study (GWAS) on neuropsychological and oculomotor traits, linked to SZ, in a general population sample of healthy young males (n = 1079). Follow‐up genotyping was performed in an identically phenotyped internal sample (n = 738) and an independent cohort of young males with comparable neuropsychological measures (n = 825). Heritability estimates were determined based on genome‐wide single‐nucleotide polymorphisms (SNPs) and potential regulatory effects on gene expression were assessed in human brain. Correlations with general cognitive ability and SZ risk polygenic scores were tested utilizing meta‐analysis GWAS results by the Cognitive Genomics Consortium (COGENT) and the Psychiatric Genomics Consortium (PGC‐SZ). The GWAS results implicated biologically relevant genetic loci encoding protein targets involved in synaptic neurotransmission, although no robust individual replication was detected and thus additional validation is required. Secondary permutation‐based analysis revealed an excess of strongly associated loci among GWAS top‐ranked signals for verbal working memory (WM) and antisaccade intra‐subject reaction time variability (empirical P 
ISSN:1552-4841
1552-485X
DOI:10.1002/ajmg.b.32323