ADHD and DAT1: further evidence of paternal over-transmission of risk alleles and haplotype

Am J Med Genet B Neuropsychiatr Genet. 2010 Jan 5;153B(1):97-102. doi: 10.1002/ajmg.b.30960.

Abstract

We [Hawi et al. (2005); Am J Hum Genet 77:958-965] reported paternal over-transmission of risk alleles in some ADHD-associated genes. This was particularly clear in the case of the DAT1 3'-UTR VNTR. In the current investigation, we analyzed three new sample comprising of 1,248 ADHD nuclear families to examine the allelic over-transmission of DAT1 in ADHD. The IMAGE sample, the largest of the three-replication samples, provides strong support for a parent of origin effect for allele 6 and the 10 repeat allele (intron 8 and 3'-UTR VNTR, respectively) of DAT1. In addition, a similar pattern of over-transmission of paternal risk haplotypes (constructed from the above alleles) was also observed. Some support is also derived from the two smaller samples although neither is independently significant. Although the mechanism driving the paternal over-transmission of the DAT risk alleles is not known, these finding provide further support for this phenomenon.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Untranslated Regions
  • Alleles*
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Genomic Imprinting*
  • Haplotypes*
  • Humans
  • Minisatellite Repeats

Substances

  • 3' Untranslated Regions
  • Dopamine Plasma Membrane Transport Proteins
  • SLC6A3 protein, human