Genome-wide association study in German patients with attention deficit/hyperactivity disorder

Am J Med Genet B Neuropsychiatr Genet. 2011 Dec;156B(8):888-97. doi: 10.1002/ajmg.b.31246. Epub 2011 Oct 19.

Abstract

The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome-wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM-IV criteria; Human660W-Quadv1; Illumina, San Diego, CA) and on 1,300 population-based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P-values (best P-value: 8.38 × 10(-7)) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P-values (P-values ≤ 7.57 × 10(-5) ) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect-size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta-analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect-size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome-wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P-values compared to SNPs within random sets of genes of the same size. We did not find genome-wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Child
  • Female
  • Genetic Markers
  • Genome-Wide Association Study*
  • Genotype
  • Germany
  • Humans
  • Male
  • Polymorphism, Single Nucleotide*
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / genetics

Substances

  • GRM5 protein, human
  • Genetic Markers
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate