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 B Neuropsychiatr Genet. 2010 Sep;153B(6):1189-99. doi: 10.1002/ajmg.b.31090.

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.

Publication types

  • Meta-Analysis

MeSH terms

  • Alleles
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Case-Control Studies
  • Family
  • Gene Frequency
  • Genetic Association Studies*
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Humans
  • Minisatellite Repeats / genetics*
  • Receptors, Dopamine D4 / genetics*

Substances

  • DRD4 protein, human
  • Receptors, Dopamine D4