HAWI, Z., Kent, L., Hill, M., Anney, R. J. L., Brookes, K-J., Barry, B., Franke, B., Banaschewski, T., Buitelaar, J., Ebstein, R. P., Miranda, A., Oades, R. D., Roeyers, H., Rothenberger, A., Sergeant, J. A., Sonuga-Barke, E. J. S., Steinhausen, H-C., Faraone, S. V., Asherson, P., & Gill, M. (2010)
ADHD and DAT1: further evidence of paternal over transmission of risk alleles and haplotype. American Journal of Medical Genetics Part B, 153B, 97-102. DOI: 10.1002/ajmg.b.30960. [Request a copy] - View Article

Background: 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.

Aims - Methods: Here we analyzed 3 new samples comprising of 1,248 ADHD nuclear families to examine the allelic over-transmission of DAT1 in ADHD.

1 - The IMAGE sample, the largest of the 3-replication samples, provides strong support for a parent-of-origin effect for allele 6 and the 10 repeat allele (intron 8 & 3-UTR VNTR, respectively) of DAT1.

2 - In addition, a similar pattern of over-transmission of paternal risk haplotypes (constructed from the above alleles) was also observed.

3 - Some support is also derived from the 2 smaller samples although neither is independently significant.

Discussion: Although the mechanism driving the paternal over-transmission of the DAT risk alleles is not known, these findings provide further support for this phenomenon.

Support NIH and the Health Research Board, Dublin