DRD4 gene variants and sustained attention in attention deficit hyperactivity disorder (ADHD)

Effects of associated alleles at the VNTR and -521 SNP

Mark A. Bellgrove, Ziarih Hawi, Naomi Lowe, Aiveen Kirley, Ian H. Robertson, Michael Gill

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

Associations between attention deficit hyperactivity disorder (ADHD) and genetic variants within the dopamine D4 receptor gene have been much reported. Variants investigated include the 7-repeat allele of a VNTR within the third exon, and two SNPs (-521 and -616) located with the promoter region. We investigated the relationship between the VNTR, -521, and -616 SNPs and sustained attention performance in 54 ADHD probands, relative to a non-genotyped control group. Participants performed the Sustained Attention to Response Task (SART) in which the response to an unpredictably occurring target digit must be inhibited. This task, therefore, challenged sustained attention and included a response inhibition component. Consistent with previous reports, ADHD participants possessing the 7-repeat allele of the VNTR outperformed those children not possessing this allele, both in terms of errors and response variability. In family based analyses, better performance on the SART tended to predict biased transmission of the 7-repeat allele from heterozygous parents. For the -521 SNP, A allele homozygotes showed greater impairment than heterozygotes or those not possessing this allele, both in terms of total errors and response variability. Family based analysis showed that higher total errors on the SART predicted transmission of the A allele from heterozygous parents. There were no effects of the -616 SNP. Our results suggest dissociable effects of the "associated alleles" of DRD4 gene variants on sustained attention: while the 7-repeat allele of the VNTR is associated with relatively better performance, the A allele of the -521 SNP is associated with poorer performance.

Original languageEnglish
Pages (from-to)81-86
Number of pages6
JournalAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume136 B
Issue number1
DOIs
Publication statusPublished - 5 Jul 2005
Externally publishedYes

Keywords

  • Attention
  • Dopamine
  • DRD4
  • Genetics

Cite this

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title = "DRD4 gene variants and sustained attention in attention deficit hyperactivity disorder (ADHD): Effects of associated alleles at the VNTR and -521 SNP",
abstract = "Associations between attention deficit hyperactivity disorder (ADHD) and genetic variants within the dopamine D4 receptor gene have been much reported. Variants investigated include the 7-repeat allele of a VNTR within the third exon, and two SNPs (-521 and -616) located with the promoter region. We investigated the relationship between the VNTR, -521, and -616 SNPs and sustained attention performance in 54 ADHD probands, relative to a non-genotyped control group. Participants performed the Sustained Attention to Response Task (SART) in which the response to an unpredictably occurring target digit must be inhibited. This task, therefore, challenged sustained attention and included a response inhibition component. Consistent with previous reports, ADHD participants possessing the 7-repeat allele of the VNTR outperformed those children not possessing this allele, both in terms of errors and response variability. In family based analyses, better performance on the SART tended to predict biased transmission of the 7-repeat allele from heterozygous parents. For the -521 SNP, A allele homozygotes showed greater impairment than heterozygotes or those not possessing this allele, both in terms of total errors and response variability. Family based analysis showed that higher total errors on the SART predicted transmission of the A allele from heterozygous parents. There were no effects of the -616 SNP. Our results suggest dissociable effects of the {"}associated alleles{"} of DRD4 gene variants on sustained attention: while the 7-repeat allele of the VNTR is associated with relatively better performance, the A allele of the -521 SNP is associated with poorer performance.",
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DRD4 gene variants and sustained attention in attention deficit hyperactivity disorder (ADHD) : Effects of associated alleles at the VNTR and -521 SNP. / Bellgrove, Mark A.; Hawi, Ziarih; Lowe, Naomi; Kirley, Aiveen; Robertson, Ian H.; Gill, Michael.

In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Vol. 136 B, No. 1, 05.07.2005, p. 81-86.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - DRD4 gene variants and sustained attention in attention deficit hyperactivity disorder (ADHD)

T2 - Effects of associated alleles at the VNTR and -521 SNP

AU - Bellgrove, Mark A.

AU - Hawi, Ziarih

AU - Lowe, Naomi

AU - Kirley, Aiveen

AU - Robertson, Ian H.

AU - Gill, Michael

PY - 2005/7/5

Y1 - 2005/7/5

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AB - Associations between attention deficit hyperactivity disorder (ADHD) and genetic variants within the dopamine D4 receptor gene have been much reported. Variants investigated include the 7-repeat allele of a VNTR within the third exon, and two SNPs (-521 and -616) located with the promoter region. We investigated the relationship between the VNTR, -521, and -616 SNPs and sustained attention performance in 54 ADHD probands, relative to a non-genotyped control group. Participants performed the Sustained Attention to Response Task (SART) in which the response to an unpredictably occurring target digit must be inhibited. This task, therefore, challenged sustained attention and included a response inhibition component. Consistent with previous reports, ADHD participants possessing the 7-repeat allele of the VNTR outperformed those children not possessing this allele, both in terms of errors and response variability. In family based analyses, better performance on the SART tended to predict biased transmission of the 7-repeat allele from heterozygous parents. For the -521 SNP, A allele homozygotes showed greater impairment than heterozygotes or those not possessing this allele, both in terms of total errors and response variability. Family based analysis showed that higher total errors on the SART predicted transmission of the A allele from heterozygous parents. There were no effects of the -616 SNP. Our results suggest dissociable effects of the "associated alleles" of DRD4 gene variants on sustained attention: while the 7-repeat allele of the VNTR is associated with relatively better performance, the A allele of the -521 SNP is associated with poorer performance.

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KW - Dopamine

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M3 - Article

VL - 136 B

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JO - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

SN - 1552-4841

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