Genetics of inhibition and error processing- implications for ADHD, schizophrenia and drug abuse

Talk given during the "Introduction to Imaging Genetics" workshop at the 2012 Organization for Human Brain Mapping (OHBM) conference in in Beijing, 10-14 June

The relationship between genotypic variation at <i>ADRA2A</i> rs1800544 and the low-frequency RT fluctuation measure Slow-5.

<p>Relative power in the Slow-5 band (%) increased with each copy of the G allele.</p

The influence of COMT/val158met and ADRA2A gene variants on low-frequency fluctuation measures Slow-4 and Slow-5.

<p>The influence of COMT/val158met and ADRA2A gene variants on low-frequency fluctuation measures Slow-4 and Slow-5.</p

TDT analysis of <i>SNAP25</i> polymorphisms in ADHD nuclear families.

<p>T =  Transmitted, NT =  Not Transmitted, * =  Empirical P-value from HAPLOVIEW assessed the gene-wide significance value estimated on the basis of 10000 permutations.</p

Allelic variation in dopamine D2 receptor gene is associated with attentional impulsiveness on the Barratt Impulsiveness Scale (BIS-11)

<p><b>Objectives:</b> Previous studies have postulated that noradrenergic and/or dopaminergic gene variations are likely to underlie individual differences in impulsiveness, however, few have shown this. The current study examined the relationship between catecholamine gene variants and self-reported impulsivity, as measured by the Barratt Impulsiveness Scale (Version 11; BIS-11)</p> <p><b>Methods:</b> Six hundred and seventy-seven non-clinical adults completed the Barratt Impulsiveness Scale (BIS-11). DNA was analysed for a set of 142 single-nucleotide polymorphisms (SNPs) across 20 autosomal catecholamine genes. Association was tested using an additive regression model with permutation testing used to control for the influence of multiple comparison.</p> <p><b>Results:</b> Analysis revealed an influence of rs4245146 of the dopamine D2 receptor (DRD2) gene on the BIS-11 attention first-order factor, such that self-reported attentional impulsiveness increased in an additive fashion with each copy of the T allele.</p> <p><b>Conclusions:</b> These findings provide preliminary evidence that allelic variation in DRD2 may influence impulsiveness by increasing the propensity for attentional lapses.</p

Linkage disequilibrium relation of previously associated ADHD-<i>SNAP25</i> variants with SNPs of this investigation.

<p>ND =  LD Not defined.</p

Haplotype analysis of <i>SNAP25</i> SNPs in ADHD nuclear families.

<p>Freq =  Haplotype frequency, T =  Transmitted, UT =  Untransmitted, * = 10000 permutation.</p

Linkage disequilibrium relation (expressed as D′ values) of <i>snap25</i> examined SNPs.

<p>Linkage disequilibrium relation (expressed as D′ values) of <i>snap25</i> examined SNPs.</p

Relative expression of SNAP25 in non- pathological samples.

<p>A and B show decreased expression with ADHD associated alleles; C and D show the level of expression relative to ADHD risk and protective haplotypes respectively. Error bars represent the standard error of the mean.</p

Dopamine transporter genotype is associated with a lateralised resistance to distraction during attention selection

<p>Supplementary Information for our manuscript, "Genetically mediated resistance to distraction: influence of dopamine transporter genotype on attentional selection"</p