INTRODUCTION: Molecular genetic research has mainly focused on the D4 dopamine receptor (DRD4) and the dopamine transporter (DAT) genes in attention-deficit hyperactivity disorder (ADHD). A recent meta-analysis showed that the DRD4 gene has a significant role in the vulnerability to ADHD. OBJECTIVES: With an equal number of positive and negative association studies between the 10-repeat of the DAT gene and ADHD, a meta-analysis is required for this other candidate gene. METHODS: We re-analysed the 13 published family-based association studies between ADHD and the DAT gene. Following recent recommendations, different biases were specifically assessed, such as the sample-size effect and the time effect. RESULTS: The meta-analysis showed no significant association between ADHD and the DAT gene (P = 0.21), but an important between-samples heterogeneity (P = 0.0009). Odds ratios above 1 are mostly observed in studies with a small number of informative transmissions, and decrease with larger sample size. CONCLUSIONS: Contrary to what was found for the DRD4 gene, the 10-repeat allele of the DAT gene has at most a minor role in the genetic susceptibility of ADHD. The different biases detected herein probably explain the initial impression of a significant impact of the DAT gene on hyperactivity.
INTRODUCTION: Molecular genetic research has mainly focused on the D4 dopamine receptor (DRD4) and the dopamine transporter (DAT) genes in attention-deficit hyperactivity disorder (ADHD). A recent meta-analysis showed that the DRD4 gene has a significant role in the vulnerability to ADHD. OBJECTIVES: With an equal number of positive and negative association studies between the 10-repeat of the DAT gene and ADHD, a meta-analysis is required for this other candidate gene. METHODS: We re-analysed the 13 published family-based association studies between ADHD and the DAT gene. Following recent recommendations, different biases were specifically assessed, such as the sample-size effect and the time effect. RESULTS: The meta-analysis showed no significant association between ADHD and the DAT gene (P = 0.21), but an important between-samples heterogeneity (P = 0.0009). Odds ratios above 1 are mostly observed in studies with a small number of informative transmissions, and decrease with larger sample size. CONCLUSIONS: Contrary to what was found for the DRD4 gene, the 10-repeat allele of the DAT gene has at most a minor role in the genetic susceptibility of ADHD. The different biases detected herein probably explain the initial impression of a significant impact of the DAT gene on hyperactivity.
Authors: Avinash V Dharmadhikari; Sung-Hae L Kang; Przemyslaw Szafranski; Richard E Person; Srirangan Sampath; Siddharth K Prakash; Patricia I Bader; John A Phillips; Vickie Hannig; Misti Williams; Sherry S Vinson; Angus A Wilfong; Tyler E Reimschisel; William J Craigen; Ankita Patel; Weimin Bi; James R Lupski; John Belmont; Sau Wai Cheung; Pawel Stankiewicz Journal: Hum Mol Genet Date: 2012-04-27 Impact factor: 6.150
Authors: Kate Langley; Tom A Fowler; Deborah L Grady; Robert K Moyzis; Peter A Holmans; Marianne B M van den Bree; Michael J Owen; Michael C O'Donovan; Anita Thapar Journal: Eur Child Adolesc Psychiatry Date: 2008-06-18 Impact factor: 4.785
Authors: Joseph Biederman; Carter R Petty; Kristina S Ten Haagen; Jacqueline Small; Alysa E Doyle; Thomas Spencer; Eric Mick; Michael C Monuteaux; Jordan W Smoller; Stephen V Faraone Journal: Psychiatry Res Date: 2009-11-10 Impact factor: 3.222