Journal
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
Volume 156B, Issue 8, Pages 888-897Publisher
WILEY
DOI: 10.1002/ajmg.b.31246
Keywords
psychiatric; children; early onset; homogeneous
Categories
Funding
- German Research Association (DFG) [He1446/9-1, KFO 125, SFB 581, GRK 1156, ME 1923/5-1, ME 1923/5-3, GRK 1389, SCHA 542/10-3]
- Bundesministerium fur Bildung und Forschung [BMBF 01GV0605]
- Medical Faculty, RWTH Aachen, Germany [EK 119/05]
- US National of Institute of Health [R13MH059126, R01MH62873, R01MH081803, K23MH066275]
- University of Pennsylvania CTR [UL1-RR-024134]
- Children's Hospital of Philadelphia
- Affymetrix Power Award
- NHMRC (Australia)
- Sidney Sax Public Health Fellowship [443036]
- UMC Utrecht Genvlag Grant
- Radboud University Nijmegen Medical Centre
- Medical Research Council [G0801418B] Funding Source: researchfish
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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 x 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 x 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. (C) 2011 Wiley Periodicals, Inc.
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