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

Ari Pinar, Ziarih Hawi, Tarrant Cummins, Beth Johnson, Marc Pauper, Janette Tong, Jeggan Tiego, Amy Finlay, Marieke Klein, Barbara Franke, Alex Fornito, Mark A. Bellgrove

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Article number207
Number of pages8
JournalTranslational Psychiatry
Volume8
Issue number1
DOIs
Publication statusPublished - 4 Oct 2018

Keywords

  • biomarkers
  • genomics

Cite this

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title = "Genome-wide association study reveals novel genetic locus associated with intra-individual variability in response time",
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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Genome-wide association study reveals novel genetic locus associated with intra-individual variability in response time. / Pinar, Ari; Hawi, Ziarih; Cummins, Tarrant; Johnson, Beth; Pauper, Marc; Tong, Janette; Tiego, Jeggan; Finlay, Amy; Klein, Marieke; Franke, Barbara; Fornito, Alex; Bellgrove, Mark A.

In: Translational Psychiatry, Vol. 8, No. 1, 207, 04.10.2018.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Genome-wide association study reveals novel genetic locus associated with intra-individual variability in response time

AU - Pinar, Ari

AU - Hawi, Ziarih

AU - Cummins, Tarrant

AU - Johnson, Beth

AU - Pauper, Marc

AU - Tong, Janette

AU - Tiego, Jeggan

AU - Finlay, Amy

AU - Klein, Marieke

AU - Franke, Barbara

AU - Fornito, Alex

AU - Bellgrove, Mark A.

PY - 2018/10/4

Y1 - 2018/10/4

N2 - 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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