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Multicenter Study
. 2010 Sep;49(9):906-20.
doi: 10.1016/j.jaac.2010.06.007. Epub 2010 Aug 5.

Case-control genome-wide association study of attention-deficit/hyperactivity disorder

Benjamin M Neale  1 , Sarah Medland, Stephan Ripke, Richard J L Anney, Philip Asherson, Jan Buitelaar, Barbara Franke, Michael Gill, Lindsey Kent, Peter Holmans, Frank Middleton, Anita Thapar, Klaus-Peter Lesch, Stephen V Faraone, Mark Daly, Thuy Trang Nguyen, Helmut Schäfer, Hans-Christoph Steinhausen, Andreas Reif, Tobias J Renner, Marcel Romanos, Jasmin Romanos, Andreas Warnke, Susanne Walitza, Christine Freitag, Jobst Meyer, Haukur Palmason, Aribert Rothenberger, Ziarih Hawi, Joseph Sergeant, Herbert Roeyers, Eric Mick, Joseph Biederman; IMAGE II Consortium Group
Collaborators, Affiliations
Multicenter Study

Case-control genome-wide association study of attention-deficit/hyperactivity disorder

Benjamin M Neale et al. J Am Acad Child Adolesc Psychiatry. 2010 Sep.

Abstract

Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genomewide association studies (GWAS) are needed.

Method: We used case-control analyses of 896 cases with DSM-IV ADHD genotyped using the Affymetrix 5.0 array and 2,455 repository controls screened for psychotic and bipolar symptoms genotyped using Affymetrix 6.0 arrays. A consensus SNP set was imputed using BEAGLE 3.0, resulting in an analysis dataset of 1,033,244 SNPs. Data were analyzed using a generalized linear model.

Results: No genome-wide significant associations were found. The most significant results implicated the following genes: PRKG1, FLNC, TCERG1L, PPM1H, NXPH1, PPM1H, CDH13, HK1, and HKDC1.

Conclusions: The current analyses are a useful addition to the present literature and will make a valuable contribution to future meta-analyses. The candidate gene findings are consistent with a prior meta-analysis in suggesting that the effects of ADHD risk variants must, individually, be very small and/or include multiple rare alleles.

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Figures

Figure 1
Figure 1
Population substructure within the case (red dots) and control (black dots) as assessed by multidimensional scaling. Note: PCA1 = first multidimensional scaling dimension
Figure 2
Figure 2
Quartile-Quartile Plot of Genome-wide Association of Attention-Deficit / Hyperactivity Disorder.
Figure 3
Figure 3
Manhattan plot from the genome wide generalized linear model (GLM) analysis. Note: ADHD = Attention-deficit / Hyperactivity Disorder; Chr = Chromosome; GWAS = Genome-wide association.
Figure 4
Figure 4
Regional association and Linkage Disequilibrium (LD) plot for the 10q21.1 region. Note: The most associated genotyped single-nucleotide polymorphism (SNP) is shown in the diamond in bright red and the color of the remaining markers reflects the linkage disequilibrium (r2) with the top SNP in each panel (increasing red hue associated with increasing r2). The recombination rate (right-hand y axis) is plotted in light blue and is based on the European-American (CEU) HapMap Phase III population.
Figure 5a
Figure 5a
Regional association and Linkage Disequilibrium (LD) plot for the 20q13.33 region
Figure 5b
Figure 5b
Regional association and Linkage Disequilibrium (LD) plot for the 7q32.1 region.
See this image and copyright information in PMC

Comment in

  • The new genetics in child psychiatry.
    Hudziak JJ, Faraone SV. Hudziak JJ, et al. J Am Acad Child Adolesc Psychiatry. 2010 Aug;49(8):729-35. doi: 10.1016/j.jaac.2010.06.010. J Am Acad Child Adolesc Psychiatry. 2010. PMID: 20643308 No abstract available.

References

    1. Faraone SV, Sergeant J, Gillberg C, Biederman J. The Worldwide Prevalence of ADHD: Is it an American Condition? World Psychiatry. 2003;2(2):104–113. - PMC - PubMed
    1. Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: Results from the national comorbidity survey replication. American Journal of Psychiatry. 2006;163(4):716–723. - PMC - PubMed
    1. Faraone SV, Biederman J. What is the prevalence of adult ADHD? Results of a population screen of 966 adults. Journal of Attention Disorders. 2005;9(2):384–391. - PubMed
    1. Faraone SV, Biederman J. Nature, nurture, and attention deficit hyperactivity disorder. Developmental Review. 2000;20:568–581.
    1. Faraone SV, Biederman J, Spencer TJ, et al. Diagnosing Adult attention deficit hyperactivity disorder: Are Late Onset and Subthreshold Diagnoses Valid? American Journal of Psychiatry. 2006;163(10):1720–1729. - PubMed

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