1. Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood
- Author
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Costas N. Stefanis, Panos Bitsios, Nicholas C. Stefanis, Dan E. Arking, Dimitrios Avramopoulos, Nikolaos Smyrnis, Pallav Bhatnagar, Alex Hatzimanolis, Panos Roussos, Anna Moes, Ruihua Wang, and Ann E. Pulver
- Subjects
cognition ,Male ,Risk ,medicine.medical_specialty ,Adolescent ,Genotype ,Population ,Genome-wide association study ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,working memory ,Young Adult ,Cellular and Molecular Neuroscience ,Genetic variation ,medicine ,GWAS ,Humans ,Genetic Predisposition to Disease ,psychosis ,education ,Research Articles ,Genetics (clinical) ,Genetics ,education.field_of_study ,Heritability ,endophenotype ,Psychiatry and Mental health ,Memory, Short-Term ,Gene Expression Regulation ,Endophenotype ,Schizophrenia ,Medical genetics ,Female ,Cognition Disorders ,Neurocognitive ,Research Article ,Genome-Wide Association Study - Abstract
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
- Published
- 2015
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