Smith TF, 201020468072
||Smith T. F. (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 B Neuropsychiatr Genet, 153B(6): 1189-99.
||Candidate association study
||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-value=0.00005) and there was significant systematic variability among studies (Q=54.24; P-value=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.
Genes reported by this study: 1