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

✍ Scribed by Taylor F. Smith

• Book ID: 101452015
• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 249 KB
• Volume: 153B
• Category: Article
• ISSN: 1552-4841
• DOI: 10.1002/ajmg.b.31090

✦ Synopsis

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. © 2010 Wiley‐Liss, Inc.