title: Meta-analysis of the heterogeneity in association of DRD4 7-repeat allele and AD/HD: stronger association with AD/HD combined type.
abstract: 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; I(2) = 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.
authors.affiliation: Department of Psychology, University of North Carolina at Greensboro, 1100 W. Market Street, Greensboro, NC 27402, USA. tfsmith2@uncg.edu
authors.forename: Taylor F
authors.initials: TF
authors.lastname: Smith
mesh_terms: D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D016022:Case-Control Studies; D005190:Family; D005787:Gene Frequency; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D018598:Minisatellite Repeats / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*
chemical_list: C493599:DRD4 protein, human; D050638:Receptors, Dopamine D4