Association of high reaction time variability with the 7-repeat allele absence appears to be the most consistent result and seems to be specific to ADHD .
Speed of processing , set-shifting and cognitive impulsiveness were less frequently investigated but seem to be altered in the 7-repeat allele carriers .
High reaction time variability seems to be the most replicated cognitive marker associated with the 10-repeat homozygosity .
BACKGROUND We review ed systematic ally the results of genetic studies investigating associations between putative susceptibility genes for attention-deficit hyperactivity disorder ( ADHD ) and neuropsychological traits relevant for this disorder .
A “line item” approach to the identification of genes involved in polygenic behavioral disorders: The Adrenergic α2A (ADRA2A) gene
The usual approach for using single base pair polymorphisms ( SNPs ) for the investigation of the genetics of behavioral disorders is to examine a single diagnostic syndrome or personality trait based on variables relating to a cluster of behavioral symptoms . However , since some of these variables may address behaviors that are associated with one allele while others are associated with the other allele , the overall association may be non‐significant and significant sub‐syndromal associations may be missed . Thus , we have reversed the process in a technique we term a “ line item ” approach . As a test of the technique we have examined the association between genotypes of a C‐ > G‐1291 Msp I promotor SNP of the ADRA2A gene and 390 individual symptoms from a structured review of DSM‐IV criteria for twelve different groups of symptoms . We examined 334 individuals consisting of controls and subjects with Tourette syndrome ( TS ) . Based on the mean scores for each genotype , those symptoms that were individually significant at α ≤ 0.05 fell into three major groups by mode of inheritance : allele 1 codominant ( 11 > 12 > 22 ) , allele 2 codominant ( 22 > 12 > 11 ) , and negative heterosis ( 12 < 11 , 22 ) . Within each mode of inheritance group , the number of symptoms that were significant for the twelve symptom clusters was compared by chi‐square analysis . This showed that symptoms were drawn from the diagnostic groups in a significantly non‐r and om fashion . Thus , the allele 1 codominant symptoms came from the anxiety , affective , schizoid , and somatization diagnostic groups ( internalizing symptoms ) ( χ2 = 80.0 , d.f . = 11 , P ≤ 0.0000001 ) , while the allele 2 codominant symptoms came from the ADHD and oppositional defiant/conduct disorder diagnostic groups ( externalizing symptoms ) ( χ2 = 81.0 , d.f . = 11 , P ≤ 0.0000001 ) . The questions that fell in the negative heterosis type of inheritance were not significantly associated with specific diagnostic groups ( P = 0.87 ) . These results showed that the ADRA2A gene was associated with symptoms of autonomic , sympathetic dysfunction from different diagnostic groups . The advantages of the “ line item ” approach include ( a ) the identification of the symptoms associated with each allele , ( b ) the identification of symptom clusters independent of DSM diagnoses , ( c ) the elucidation of heterosis and other mode of inheritance effects , ( d ) the distinction between an association with a primary disorder versus a comorbid disorder , ( e ) the identification of associations with sub‐syndromal symptom clusters that do meet full DSM‐IV criteria , and ( f ) the identification of symptom clusters across data bases . © 2003 Wiley‐Liss ,
Association of high reaction time variability with the 7-repeat allele absence appears to be the most consistent result and seems to be specific to ADHD .
Speed of processing , set-shifting and cognitive impulsiveness were less frequently investigated but seem to be altered in the 7-repeat allele carriers .
High reaction time variability seems to be the most replicated cognitive marker associated with the 10-repeat homozygosity .
BACKGROUND We review ed systematic ally the results of genetic studies investigating associations between putative susceptibility genes for attention-deficit hyperactivity disorder ( ADHD ) and neuropsychological traits relevant for this disorder .