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Genome‐wide association study in German patients with attention deficit/hyperactivity disorder
Author(s) -
Hinney Anke,
Scherag André,
Jarick Ivonne,
Albayrak Özgür,
Pütter Carolin,
Pechlivanis Sonali,
Dauvermann Maria R.,
Beck Sebastian,
Weber Heike,
Scherag Susann,
Nguyen Trang T.,
Volckmar AnnaLena,
Knoll Nadja,
Faraone Stephen V.,
Neale Benjamin M.,
Franke Barbara,
Cichon Sven,
Hoffmann Per,
Nöthen Markus M.,
Schreiber Stefan,
Jöckel KarlHeinz,
Wichmann H.Erich,
Freitag Christine,
Lempp Thomas,
Meyer Jobst,
Gilsbach Susanne,
HerpertzDahlmann Beate,
Sinzig Judith,
Lehmkuhl Gerd,
Renner Tobias J.,
Warnke Andreas,
Romanos Marcel,
Lesch KlausPeter,
Reif Andreas,
Schimmelmann Benno G.,
Hebebrand Johannes
Publication year - 2011
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.31246
Subject(s) - german , attention deficit hyperactivity disorder , genome wide association study , association (psychology) , attention deficit , psychology , psychiatry , medicine , clinical psychology , genetics , biology , psychotherapist , genotype , gene , linguistics , philosophy , single nucleotide polymorphism
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. © 2011 Wiley Periodicals, Inc.