Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Dec 5;147B(8):1337-44.
doi: 10.1002/ajmg.b.30866.

Genome-wide association scan of attention deficit hyperactivity disorder

Benjamin M Neale  1 , Jessica Lasky-Su, Richard Anney, Barbara Franke, Kaixin Zhou, Julian B Maller, Alejandro Arias Vasquez, Philip Asherson, Wai Chen, Tobias Banaschewski, Jan Buitelaar, Richard Ebstein, Michael Gill, Ana Miranda, Robert D Oades, Herbert Roeyers, Aribert Rothenberger, Joseph Sergeant, Hans Christoph Steinhausen, Edmund Sonuga-Barke, Fernando Mulas, Eric Taylor, Nan Laird, Christoph Lange, Mark Daly, Stephen V Faraone
Affiliations

Genome-wide association scan of attention deficit hyperactivity disorder

Benjamin M Neale et al. Am J Med Genet B Neuropsychiatr Genet. .

Abstract

Results of behavioral genetic and molecular genetic studies have converged to suggest that genes substantially contribute to the development of attention deficit/hyperactivity disorder (ADHD), a common disorder with an onset in childhood. Yet, despite numerous linkage and candidate gene studies, strongly consistent and replicable association has eluded detection. To search for ADHD susceptibility genes, we genotyped approximately 600,000 SNPs in 958 ADHD affected family trios. After cleaning the data, we analyzed 438,784 SNPs in 2,803 individuals comprising 909 complete trios using ADHD diagnosis as phenotype. We present the initial TDT findings as well as considerations for cleaning family-based TDT data. None of the SNP association tests achieved genome-wide significance, indicating that larger samples may be required to identify risk loci for ADHD. We additionally identify a systemic bias in family-based association, and suggest that variable missing genotype rates may be the source of this bias.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Power to detect at least 1 genome-wide significant association for 909 trios
From top to bottom the series are based on models with an OR of 1.3 and MAF of 0.40, OR of 1.3 and MAF of 0.20, OR of 1.2 and MAF of 0.40, OR of 1.2 and MAF of 0.20. The power to detect at least one locus is equal to 1 − (1 − Q)N where Q is the power to detect an association at significance level of 5x10-8 of a given model and N is the number of loci with said effect.
Figure 2
Figure 2
The QQ Plot of the TDT χ2 from the genome-wide data
Figure 3
Figure 3
Distribution of P values for selected candidate genes
See this image and copyright information in PMC

References

    1. Altshuler D, Daly M. Guilt beyond a reasonable doubt. Nat Genet. 2007;39(7):813–5. - PubMed
    1. American Psychiatric A. Diagnostic and statistical manual of mental disorders: DSM-III-R. Washington, D.C: American Psychiatric Association; 1987. p. 567. %7 3rd-Revised p.
    1. Anney R, Kenny E, O’Dushlaine C, Lasky-Su J, Franke B, Asherson P, Morris DW, Neale B, Asherson P, Faraone SV, et al. Non-Random Error in Genotype Calling Procedures: implications for family-based and case-control genome-wide association studies submitted. - PMC - PubMed
    1. Arcos-Burgos M, Castellanos FX, Pineda D, Lopera F, David Palacio J, Guillermo Palacio L, Rapoport JL, Berg K, Bailey-Wilson JE, Muenke M. Attention-deficit/hyperactivity disorder in a population isolate: linkage to Loci at 4q13.2, 5q33.3, 11q22, and 17p11. Am J Hum Genet. 2004;75(6):998–1014. - PMC - PubMed
    1. Asherson P, Zhou K, Anney RJ, Franke B, Buitelaar J, Ebstein R, Gill M, Altink M, Arnold R, Boer F, et al. A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16. Mol Psychiatry. 2008;13(5):514–21. - PubMed

Publication types