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Examination of the current top candidate genes for AD in a genome-wide association study

Molecular Psychiatry volume 15, pages 756–766 (2010)Cite this article

Abstract

With the advent of technologies that allow simultaneous genotyping of thousands of single-nucleotide polymorphisms (SNPs) across the genome, the genetic contributions to complex diseases can be explored at an unprecedented detail. This study is among the first to apply the genome-wide association study (GWAS) approach to Alzheimer disease (AD). We present our GWAS results from the German population for genes included in the ‘Top Results’ list on the AlzGene database website. In addition to the apolipoprotein E locus, we identified nominally significant association signals in six of the ten genes investigated, albeit predominantly for SNPs other than those already published as being disease associated. Further, all of the four AD genes previously identified through GWAS also showed nominally significant association signals in our data. The results of our comparative study reinforce the necessity for replication and validation, not only of GWAS but also of candidate gene case–control studies, in different populations. Furthermore, cross-platform comparison of genotyping results can also identify new association signals. Finally, our data confirm that GWAS, regardless of the platform, are valuable for the identification of genetic variants associated with AD.

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Acknowledgements

We wish to thank all participants of this study for their contribution. Tamara Eisele and all staff at the dementia outpatient unit are acknowledged for their help in the collection and processing of samples. This work was funded by the German National Genome Research Network and the German Ministry for Education and Research (Grant Number 01GS0465 (MR)).

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Author notes

  1. T M Feulner and S M Laws: These authors contributed equally to this paper.

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Neurochemistry and Neurogenetics Laboratory, Technische Universität München (TUM), Munich, Germany

    T M Feulner, S M Laws, P Friedrich, C Riehle & M Riemenschneider

  2. Centre of Excellence for Alzheimer's Disease Research and Care, Sir James McCusker Alzheimer's Disease Research Unit, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia

    S M Laws

  3. Department of Medical Statistics and Epidemiology, Technische Universität München (TUM), Munich, Germany

    S Wagenpfeil, S H R Wurst, C Riehle & K A Kuhn

  4. Institute of Medical Informatics and Statistics, Christian-Albrechts-University, Kiel, Germany

    M Krawczak

  5. Department of General Internal Medicine, Biobank Popgen, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany

    M Krawczak & S Schreiber

  6. Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany

    S Schreiber & S Nikolaus

  7. Department of Psychiatry and Psychotherapy, Technische Universität München (TUM), Munich, Germany

    H Förstl, A Kurz & M Riemenschneider

  8. Department of Psychiatry and Psychotherapy, Universität des Saarlandes, Homburg/Saar, Germany

    M Riemenschneider

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  1. T M Feulner
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Correspondence to M Riemenschneider.

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Feulner, T., Laws, S., Friedrich, P. et al. Examination of the current top candidate genes for AD in a genome-wide association study. Mol Psychiatry 15, 756–766 (2010). https://doi.org/10.1038/mp.2008.141

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