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Transl Psychiatry. 2018 Oct 4;8(1):207. doi: 10.1038/s41398-018-0262-z.

Genome-wide association study reveals novel genetic locus associated with intra-individual variability in response time.

Author information

1
School of Psychological Sciences and Monash Institute for Cognitive and Clinical Neurosciences (MICCN), Monash University, Melbourne, VIC, Australia.
2
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
3
Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
4
Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.
5
School of Psychological Sciences and Monash Institute for Cognitive and Clinical Neurosciences (MICCN), Monash University, Melbourne, VIC, Australia. mark.bellgrove@monash.edu.

Abstract

Intra-individual response time variability (IIRTV) is proposed as a viable endophenotype for many psychiatric disorders, particularly attention-deficit hyperactivity disorder (ADHD). Here we assessed whether IIRTV was associated with common DNA variation genome-wide and whether IIRTV mediated the relationship between any associated loci and self-reported ADHD symptoms. A final data set from 857 Australian young adults (489 females and 368 males; Mage = 22.14 years, SDage = 4.82 years) who completed five response time tasks and self-reported symptoms of ADHD using the Conners' Adult ADHD Rating Scale was used. Principal components analysis (PCA) on these response time measures (standard deviation of reaction times and the intra-individual coefficient of variation) produced two variability factors (labelled response selection and selective attention). To understand the genetic drivers of IIRTV we performed a genome-wide association analysis (GWAS) on these PCA-derived indices of IIRTV. For the selective attention variability factor, we identified one single-nucleotide polymorphism (SNP) attaining genome-wide significance; rs62182100 in the HDAC4 gene located on chromosome 2q37. A bootstrapping mediation analysis demonstrated that the selective attention variability factor mediated the relationship between rs62182100 and self-reported ADHD symptoms. Our findings provide the first evidence of a genome-wide significant SNP association with IIRTV and support the potential utility of IIRTV as a valid endophenotype for ADHD symptoms. However, limitations of this study suggest that these observations should be interpreted with caution until replication samples become available.

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