Evidence of Common Genetic Overlap Between Schizophrenia and Cognition.

Schizophr Bull
Authors
Keywords
Abstract

Cognitive impairment is a core feature of schizophrenia but there is limited understanding of the genetic relationship between cognition in the general population and schizophrenia. We examine how common variants associated with schizophreniaen massecontribute to childhood cognitive ability in a population-based sample, and the extent to which common genetic variants associated with childhood cognition explain variation in schizophrenia. Schizophrenia polygenic risk scores were derived from the Psychiatric Genomics Consortium (n= 69 516) and tested for association with IQ, attention, processing speed, working memory, problem solving, and social cognition in over 5000 children aged 8 from the Avon Longitudinal Study of Parents and Children birth cohort. Polygenic scores for these cognitive domains were tested for association with schizophrenia in a large UK schizophrenia sample (n= 11 853). Bivariate genome-wide complex trait analysis (GCTA) estimated the amount of shared genetic factors between schizophrenia and cognitive domains. Schizophrenia polygenic risk score was associated with lower performance IQ (P= .001) and lower full IQ (P= .013). Polygenic score for performance IQ was associated with increased risk for schizophrenia (P= 3.56E-04). Bivariate GCTA revealed moderate genetic correlation between schizophrenia and both performance IQ (rG= -.379,P= 6.62E-05) and full IQ (rG= -.202,P= 5.00E-03), with approximately 14% of the genetic component of schizophrenia shared with that for performance IQ. Our results support the presence of shared common genetic factors between schizophrenia and childhood cognitive ability. We observe a genetic relationship between schizophrenia and performance IQ but not verbal IQ or other cognitive variables, which may have implications for studies utilizing cognitive endophenotypes for psychosis.

Year of Publication
2016
Journal
Schizophr Bull
Volume
42
Issue
3
Pages
832-42
Date Published
2016 May
ISSN
1745-1701
URL
DOI
10.1093/schbul/sbv168
PubMed ID
26678674
PubMed Central ID
PMC4838093
Links
Grant list
102215 / Wellcome Trust / United Kingdom
MC_PC_15018 / Medical Research Council / United Kingdom
74882 / Medical Research Council / United Kingdom
MR/M006727/1 / Medical Research Council / United Kingdom
076467 / Wellcome Trust / United Kingdom
MR/K004360/1 / Medical Research Council / United Kingdom
MR/L010305/1 / Medical Research Council / United Kingdom
G0800509 / Medical Research Council / United Kingdom