1. ¹Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Technische Universität München (TUM), Munich, Germany
2. ²Centre 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
3. ³Department of Medical Statistics and Epidemiology, Technische Universität München (TUM), Munich, Germany
4. ⁴Institute of Medical Informatics and Statistics, Christian-Albrechts-University, Kiel, Germany
5. ⁵Biobank Popgen, Department of General Internal Medicine, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany
6. ⁶Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany
7. ⁷Department of Psychiatry and Psychotherapy, Technische Universität München (TUM), Munich, Germany
8. ⁸Department of Psychiatry and Psychotherapy, Universität des Saarlandes, Homburg/Saar, Germany

Correspondence: Dr M Riemenschneider, Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Technische Universität München (TUM), Ismaningerstrasse 22, 81675 Munich, Germany. E-mail: m.riemenschneider@lrz.tum.de

⁹These authors contributed equally to this paper.

Received 10 October 2008; Revised 20 November 2008; Accepted 25 November 2008; Published online 6 January 2009.

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.