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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Genome-wide association study in 404,302 individuals identifies 7 significant loci for reaction time variability
Molecular Psychiatry, Year 2023
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Description
Reaction time variability (RTV), reflecting fluctuations in response time on cognitive tasks, has been proposed as an endophenotype for many neuropsychiatric disorders. There have been no large-scale genome-wide association studies (GWAS) of RTV and little is known about its genetic underpinnings. Here, we used data from the UK Biobank to conduct a GWAS of RTV in participants of white British ancestry (n = 404,302) as well as a trans-ancestry GWAS meta-analysis (n = 44,873) to assess replication. We found 161 genome-wide significant single nucleotide polymorphisms (SNPs) distributed across 7 genomic loci in our discovery GWAS. Functional annotation of the variants implicated genes involved in synaptic function and neural development. The SNP-based heritability (h 2SNP) estimate for RTV was 3%. We investigated genetic correlations between RTV and selected neuropsychological traits using linkage disequilibrium score regression, and found significant correlations with several traits, including a positive correlation with mean reaction time and schizophrenia. Despite the high genetic correlation between RTV and mean reaction time, we demonstrate distinctions in the genetic underpinnings of these traits. Lastly, we assessed the predictive ability of a polygenic score (PGS) for RTV, calculated using PRSice and PRS-CS, and found that the RTV-PGS significantly predicted RTV in independent cohorts, but that the generalisability to other ancestry groups was poor. These results identify genetic underpinnings of RTV, and support the use of RTV as an endophenotype for neurological and psychiatric disorders. © 2023, The Author(s).
Authors & Co-Authors
Wootton, Olivia
South Africa, Cape Town
University of Cape Town
Shadrin, Alexey A.
Norway, Oslo
Universitetet I Oslo
Susser, Ezra S.
United States, New York
Columbia University
United States, New York
New York State Psychiatric Institute
Ramesar, Rajkumar S.
South Africa, Tygerberg
South African Medical Research Council
Andreassen, Ole Andreas
Norway, Oslo
Universitetet I Oslo
Stein, Dan J.
South Africa, Cape Town
University of Cape Town
South Africa, Cape Town
Sa Mrc Unit on Risk and Resilience in Mental Disorders
Dalvie, Shareefa
South Africa, Tygerberg
South African Medical Research Council
Statistics
Citations: 1
Authors: 7
Affiliations: 7
Identifiers
Doi:
10.1038/s41380-023-02292-9
ISSN:
13594184
Research Areas
Genetics And Genomics
Mental Health
Study Design
Cohort Study
Study Approach
Systematic review