Zhou, K., Chen, W., Buitelaar, J. K., Banaschewski, T., Oades, R. D., Franke, B., Sonuga-Barke, E. J. S., Ebstein, R. P., Eisenberg, J., Gill, M., Manor, I., Miranda, A., Mulas, F., Roeyers, H., Rothenberger, A., Sergeant, J. A., Steinhausen, H-C., Lasky-Su, J., Taylor, E. A., Brookes, K-J., Xu, X., Neale, B. M., Rijsdijk, F., Thompson, M. J., Asherson, P., & Faraone, S. V.

Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD. (2008) Am J Med Genet Part B. 147B, 1481-1487.DOI: 10.1002/ajmg.b.30644. (request a copy) View Article

Introduction: Associations between ADHD & 10-repeat allele of a VNTR in the 3'-untranslated region of the DA transporter gene (DAT1) are remarkably variable. A possible-reason for heterogeneous findings is comorbidity of conduct disorder (CD) -- this might indicate a distinct genetic form of ADHD (Christiansen et al., 2008)

Methods: HERE selected 576 DSM-IV combined type ADHD trios (141 with comorbid CD) from the IMAGE study to test whether DAT1 has a different effect size in the co-morbid group.

Results:
1) Our heterogeneity test result suggests that DAT1 has a significantly greater genetic influence on ADHD children without CD compared to the comorbid group.
2) The 2 significant SNPs (rs40184, rs2652511) from association tests in the ADHD-CD group also show significant genetic heterogeneity (p=0.016 & p=0.023). In addition, rs27072 shows significant heterogeneity (p=0.034), but has only a marginal association with ADHD-CD group (p=0.06) and no association with the ADHD+CD group (p=0.168).
3) Further work is needed to replicate this finding.
4) The ADHD genetic heterogeneity identified in this study can partially explain the heterogeneous association findings in previous DAT1 studies and it also emphasizes the importance of selecting genetically homogeneous samples for molecular genetic analysis of ADHD: see also Christiansen et al., 2008.

Support: NIH.