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

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Author(s)

Anke Hinney, André Scherag, Ivonne Jarick, Özgür Albayrak, Carolin Pütter, Sonali Pechlivanis, Maria R Dauvermann, Sebastian Beck, Heike Weber, Susann Scherag, Trang T Nguyen, Anna-Lena Volckmar, Nadja Knoll, Stephen V Faraone, Benjamin M Neale, Barbara Franke, Sven Cichon, Per Hoffmann, Markus M Nöthen, Stefan Schreiber & 18 others Karl-Heinz Jöckel, H-Erich Wichmann, Christine Freitag, Thomas Lempp, Jobst Meyer, Susanne Gilsbach, Beate Herpertz-Dahlmann, Judith Sinzig, Gerd Lehmkuhl, Tobias J Renner, Andreas Warnke, Marcel Romanos, Klaus-Peter Lesch, Andreas Reif, Benno G Schimmelmann, Johannes Hebebrand, Psychiatric GWAS Consortium: ADHD Subgroup, Lindsey Kent

School/Research organisations

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.
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Original languageEnglish
Pages (from-to)888-97
Number of pages10
JournalAmerican Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Volume156B
Issue number8
DOIs
Publication statusPublished - Dec 2011

    Research areas

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

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ID: 140340935