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

Hinney, A.; Scherag, A.; Jarick, I.; Albayrak, o.; Putter, 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.; Nothen, M.M.; Schreiber, S.; ... (2011). Genome-wide association study in German patients with attention deficit/hyperactivity disorder. American journal of medical genetics. Part B - Neuropsychiatric genetics, 156B(8), pp. 888-897. Hoboken, N.J.: Wiley-Liss 10.1002/ajmg.b.31246

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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 × 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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > University Psychiatric Services > University Hospital of Child and Adolescent Psychiatry and Psychotherapy
UniBE Contributor:	Schimmelmann, Benno Karl Edgar
ISSN:	1552-4841
Publisher:	Wiley-Liss
Language:	English
Submitter:	Myriam Pyrlik
Date Deposited:	04 Oct 2013 14:18
Last Modified:	05 Dec 2022 14:05
Publisher DOI:	10.1002/ajmg.b.31246
PubMed ID:	22012869
Web of Science ID:	000297222700002
URI:	https://boris.unibe.ch/id/eprint/5790 (FactScience: 210624)