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

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, Anna-Lena, Knoll, Nadja, Faraone, Stephen V., Neale, Benjamin M., Franke, Barbara, Cichon, Sven, Hoffmann, Per, Nöthen, Markus M., Schreiber, Stefan, Jöckel, Karl-Heinz, Wichmann, H.-Erich, Freitag, Christine, Lempp, Thomas, Meyer, Jobst, Gilsbach, Susanne, Herpertz-Dahlmann, Beate, Sinzig, Judith, Lehmkuhl, Gerd, Renner, Tobias J., Warnke, Andreas, Romanos, Marcel, Lesch, Klaus-Peter, Reif, Andreas, Schimmelmann, Benno G., Hebebrand, Johannes, Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Langley, Kate ORCID: https://orcid.org/0000-0002-2033-2657, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Thapar, Anita ORCID: https://orcid.org/0000-0002-3689-737X and Williams, Nigel Melville ORCID: https://orcid.org/0000-0003-1177-6931 2011. Genome-wide association study in German patients with attention deficit/hyperactivity disorder. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 156 (8) , pp. 888-897. 10.1002/ajmg.b.31246

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Systems Immunity Research Institute (SIURI) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Additional Information:	Holmans; Peter, Langley; Kate, O'Donovan; Michael, Owen; Michael, Thapar; Anita, Williams; Nigel are collaborators on this article.
Publisher:	Wiley-Blackwell
ISSN:	1552-4841
Last Modified:	17 Nov 2022 11:52
URI:	https://orca.cardiff.ac.uk/id/eprint/79923

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