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Hinney, A; Scherag, A; Jarick, I; Albayrak, Ö; Pütter, C; Pechlivanis, S; Dauvermann, M R; Beck, S; Weber, H; Scherag, S; Nguyen, T T; Volckmar, A L; Knoll, N; Faraone, S V; Neale, B M; Franke, B; Cichon, S; Hoffmann, P; Nöthen, M M; Schreiber, S; Jöckel, K H; Wichmann, H E; Freitag, C; Lempp, T; Meyer, J; Gilsbach, S; Herpertz-Dahlmann, B; Sinzig, J; Lehmkuhl, G; Renner, T J; Warnke, A; Romanos, M; Lesch, K P; Reif, A; Schimmelmann, B G; Hebebrand, J; Psychiatric GWAS Consortium, ADHD subgroup (2011). Genome-wide association study in German patients with attention deficit/hyperactivity disorder. American Journal of Medical Genetics. Part B, 156B(8):888-897.

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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.

Contributors:Psychiatric GWAS Consortium, ADHD Subgroup
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
DDC:610 Medicine & health
Language:English
Date:2011
Deposited On:24 Jan 2012 19:23
Last Modified:27 Nov 2013 23:41
Publisher:Wiley-Blackwell
ISSN:1552-4841
Publisher DOI:10.1002/ajmg.b.31246
PubMed ID:22012869
Citations:Web of Science®. Times Cited: 17
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Scopus®. Citation Count: 18

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