Alpha-2A adrenergic receptor gene variants are associated with increased intra-individual variability in response time

Tarrant Cummins, Oscar Jacoby, Ziarih Hawi, L Sanjay Nandam, Mark A V Byrne, Bung-Nyun Kim, Joseph Wagner, Christopher D Chambers, Mark Andrew Bellgrove

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Abstract

Intra-individual variability in response time has been proposed as an important endophenotype for attention deficit hyperactivity disorder (ADHD). Here we asked whether intra-individual variability is predicted by common variation in catecholamine genes and whether it mediates the relationship between these gene variants and self-reported ADHD symptoms. A total of 402 non-clinical Australian adults of European descent completed a battery of five cognitive tasks and the Conners? Adult ADHD Rating Scale. Exclusion criteria included the presence of major psychiatric or neurologic illnesses and substance dependency. A total of 21 subjects were excluded due to incomplete data or poor quality cognitive or genotyping data. The final sample comprised 381 subjects (201 males; mean age=21.2 years, s.d.=5.1 years). Principal components analysis on variability measures yielded two factors (response selection variability vs selective attention variability). Association of these factors with catecholamine gene variants was tested using single-step linear regressions, with multiple comparisons controlled using permutation analysis. The response selection variability factor was associated with two ADRA2A single-nucleotide polymorphisms (SNPs) (rs1800544, rs602618), pcorrected=0.004, 0.012, respectively, whereas the selective attention variability factor was associated with a TH SNP (rs3842727), pcorrected=0.024. A bootstrapping analysis indicated that the response selection variability factor mediated the relationship between the ADRA2A SNP rs1800544 and self-reported ADHD symptoms. Thus this study finds evidence that DNA variation in the ADRA2A gene may be causally related to ADHD-like behaviors, in part through its influence on intra-individual variability. Evidence was also found for a novel association between a TH gene variant and intra-individual variability.
Original languageEnglish
Pages (from-to)1031 - 1036
Number of pages6
JournalMolecular Psychiatry
Volume19
DOIs
Publication statusPublished - 2014

Cite this

Cummins, Tarrant ; Jacoby, Oscar ; Hawi, Ziarih ; Nandam, L Sanjay ; Byrne, Mark A V ; Kim, Bung-Nyun ; Wagner, Joseph ; Chambers, Christopher D ; Bellgrove, Mark Andrew. / Alpha-2A adrenergic receptor gene variants are associated with increased intra-individual variability in response time. In: Molecular Psychiatry. 2014 ; Vol. 19. pp. 1031 - 1036.
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title = "Alpha-2A adrenergic receptor gene variants are associated with increased intra-individual variability in response time",
abstract = "Intra-individual variability in response time has been proposed as an important endophenotype for attention deficit hyperactivity disorder (ADHD). Here we asked whether intra-individual variability is predicted by common variation in catecholamine genes and whether it mediates the relationship between these gene variants and self-reported ADHD symptoms. A total of 402 non-clinical Australian adults of European descent completed a battery of five cognitive tasks and the Conners? Adult ADHD Rating Scale. Exclusion criteria included the presence of major psychiatric or neurologic illnesses and substance dependency. A total of 21 subjects were excluded due to incomplete data or poor quality cognitive or genotyping data. The final sample comprised 381 subjects (201 males; mean age=21.2 years, s.d.=5.1 years). Principal components analysis on variability measures yielded two factors (response selection variability vs selective attention variability). Association of these factors with catecholamine gene variants was tested using single-step linear regressions, with multiple comparisons controlled using permutation analysis. The response selection variability factor was associated with two ADRA2A single-nucleotide polymorphisms (SNPs) (rs1800544, rs602618), pcorrected=0.004, 0.012, respectively, whereas the selective attention variability factor was associated with a TH SNP (rs3842727), pcorrected=0.024. A bootstrapping analysis indicated that the response selection variability factor mediated the relationship between the ADRA2A SNP rs1800544 and self-reported ADHD symptoms. Thus this study finds evidence that DNA variation in the ADRA2A gene may be causally related to ADHD-like behaviors, in part through its influence on intra-individual variability. Evidence was also found for a novel association between a TH gene variant and intra-individual variability.",
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Alpha-2A adrenergic receptor gene variants are associated with increased intra-individual variability in response time. / Cummins, Tarrant; Jacoby, Oscar; Hawi, Ziarih; Nandam, L Sanjay; Byrne, Mark A V; Kim, Bung-Nyun; Wagner, Joseph; Chambers, Christopher D; Bellgrove, Mark Andrew.

In: Molecular Psychiatry, Vol. 19, 2014, p. 1031 - 1036.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Nandam, L Sanjay

AU - Byrne, Mark A V

AU - Kim, Bung-Nyun

AU - Wagner, Joseph

AU - Chambers, Christopher D

AU - Bellgrove, Mark Andrew

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AB - Intra-individual variability in response time has been proposed as an important endophenotype for attention deficit hyperactivity disorder (ADHD). Here we asked whether intra-individual variability is predicted by common variation in catecholamine genes and whether it mediates the relationship between these gene variants and self-reported ADHD symptoms. A total of 402 non-clinical Australian adults of European descent completed a battery of five cognitive tasks and the Conners? Adult ADHD Rating Scale. Exclusion criteria included the presence of major psychiatric or neurologic illnesses and substance dependency. A total of 21 subjects were excluded due to incomplete data or poor quality cognitive or genotyping data. The final sample comprised 381 subjects (201 males; mean age=21.2 years, s.d.=5.1 years). Principal components analysis on variability measures yielded two factors (response selection variability vs selective attention variability). Association of these factors with catecholamine gene variants was tested using single-step linear regressions, with multiple comparisons controlled using permutation analysis. The response selection variability factor was associated with two ADRA2A single-nucleotide polymorphisms (SNPs) (rs1800544, rs602618), pcorrected=0.004, 0.012, respectively, whereas the selective attention variability factor was associated with a TH SNP (rs3842727), pcorrected=0.024. A bootstrapping analysis indicated that the response selection variability factor mediated the relationship between the ADRA2A SNP rs1800544 and self-reported ADHD symptoms. Thus this study finds evidence that DNA variation in the ADRA2A gene may be causally related to ADHD-like behaviors, in part through its influence on intra-individual variability. Evidence was also found for a novel association between a TH gene variant and intra-individual variability.

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