TY - JOUR
T1 - The short DRD4 repeats confer risk to attention deficit hyperactivity disorder in a family-based design and impair performance on a continuous performance test (TOVA)
AU - Manor, I.
AU - Tyano, S.
AU - Eisenberg, J.
AU - Bachner-Melman, R.
AU - Kotler, M.
AU - Ebstein, R. P.
N1 - Funding Information:
This research was supported by a grant from the Israeli Ministry of Health.
PY - 2002
Y1 - 2002
N2 - One particular candidate gene, the dopamine D4 receptor (DRD4), has been the focus of intense study regarding ADHD since the original investigation by La Hoste et al, an observation confirmed by a recent metaanalysis. However, two previous studies from Israel failed to observe this association. We have now recruited an additional sample and, overall, in the combined sample of 178 triads we observe using the transmission disequilibrium test, preferential transmission of the short allele. Additionally, we now report the effect of the DRD4 repeat region on the Test Of Variables of Attention (TOVA), a widely used computerized continuous performance test. Probands with the short exon III repeat performed significantly worse on the TOVA measured both by errors of commission and response time variable. Intriguingly, a 'dose effect' was observed. Increasing repeat size is accompanied by a reduced number of errors of commission and a significant difference is observed between the 2 vs 7 repeats. On the whole, our results lend credence to the notion that the relationship between the DRD4 receptor and ADHD is complex and may be reflecting linkage disequilibrium between the 7 or long DRD4 exon III repeats and a 'true' risk allele in this gene or a neighboring locus.
AB - One particular candidate gene, the dopamine D4 receptor (DRD4), has been the focus of intense study regarding ADHD since the original investigation by La Hoste et al, an observation confirmed by a recent metaanalysis. However, two previous studies from Israel failed to observe this association. We have now recruited an additional sample and, overall, in the combined sample of 178 triads we observe using the transmission disequilibrium test, preferential transmission of the short allele. Additionally, we now report the effect of the DRD4 repeat region on the Test Of Variables of Attention (TOVA), a widely used computerized continuous performance test. Probands with the short exon III repeat performed significantly worse on the TOVA measured both by errors of commission and response time variable. Intriguingly, a 'dose effect' was observed. Increasing repeat size is accompanied by a reduced number of errors of commission and a significant difference is observed between the 2 vs 7 repeats. On the whole, our results lend credence to the notion that the relationship between the DRD4 receptor and ADHD is complex and may be reflecting linkage disequilibrium between the 7 or long DRD4 exon III repeats and a 'true' risk allele in this gene or a neighboring locus.
KW - Association
KW - Attention deficit hyperactivity disorder
KW - Complex genetic
KW - Continuous performance test
KW - Dopamine D4 receptor
KW - Neuropsychological functioning
KW - Polymorphism
KW - TOVA
KW - Transmission disequilibrium test
UR - http://www.scopus.com/inward/record.url?scp=0036360656&partnerID=8YFLogxK
U2 - 10.1038/sj.mp.4001078
DO - 10.1038/sj.mp.4001078
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C2 - 12192625
AN - SCOPUS:0036360656
SN - 1359-4184
VL - 7
SP - 790
EP - 794
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 7
ER -