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Meta-analysis of the heterogeneity in association of DRD4 7-repeat allele and AD/HD: Stronger association with AD/HD combined type


  • Taylor F. Smith

    Corresponding author
    1. Department of Psychology, University of North Carolina at Greensboro, Greensboro, North Carolina
    • AD/HD Clinic at UNCG, University of North Carolina at Greensboro, 1100 W. Market St. 3rd Floor, P.O. Box 26170, Greensboro, NC 27402.
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  • How to Cite this Article: Smith TF. 2010. Meta-Analysis of the Heterogeneity in Association of DRD4 7-Repeat Allele and AD/HD: Stronger Association With AD/HD Combined Type. Am J Med Genet Part B 153B:1189–1199.


The purpose of this meta-analysis was to examine whether association studies between attention deficit/hyperactivity disorder (AD/HD) and the dopamine receptor 4 gene 7-repeat (DRD4 7R) allele vary systematically based on study characteristics. A total of 27 empirical studies with 28 distinct samples using either case–control or family-based association analyses were included. Consistent with previous meta-analytic work [Gizer et al. (2009), Hum Genet 126:51–90], the DRD4 7R allele was associated with AD/HD across studies (OR = 1.33; 95% CI = 1.16–1.53, z = 4.04, P = 0.00005) and there was significant systematic variability among studies (Q = 54.24; P = 0.001; I2 = 50.22). To account for the variability among studies, sample and study level covariates were examined. No differences in overall effect size emerged between family-based and case–control studies. However, the risk allele frequency in the control population accounted for a significant portion of the variance in overall effect size within case–control studies. In addition, evidence for the association between the DRD4 7R allele and distinct AD/HD subtypes emerged across family-based and case–control studies. The proportion of AD/HD, combined type individuals within the AD/HD sample was associated with a significant increase in the magnitude of association between the DRD4 7R allele and AD/HD. Conversely, an increase in the proportion of AD/HD, predominantly inattentive type individuals within the AD/HD sample was associated with a decrease in study effect size. Implications regarding AD/HD etiological and phenotypic heterogeneity are discussed. © 2010 Wiley-Liss, Inc.