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

作者：Cummins T D R; Jacoby O; Hawi Z; Nandam L S; Byrne M A V; Kim B N; Wagner J; Chambers C D; Bellgrove M A^*

来源：Molecular Psychiatry, 2014, 19(9): 1031-1036.

DOI：10.1038/mp.2013.140

• attention
• dopamine
• executive
• genetics
• ICV
• noradrenaline

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%26apos; 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), p(corrected) = 0.004, 0.012, respectively, whereas the selective attention variability factor was associated with a TH SNP (rs3842727), p(corrected) = 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.

• 出版日期2014-9