F4‐01‐01: Genome‐wide screening for novel Alzheimer's disease genes: What have we found?

not available. F4-01-02 ALZHEIMER’S DISEASE GENETICS: CURRENT STATUS AND FUTURE PERSPECTIVES Lars Bertram, Max-Planck Institute for Molecular Genetics, Berlin, Germany. Contact e-mail: lbertram@molgen.mpg.de Background: Alzheimer’s disease (AD) is a genetically complex disease whose pathogenesis is largely influenced by genetic factors. Three decades of intensive research have yielded four established AD genes (APP, PSEN1, PSEN2, APOE), and hundreds of potential susceptibility loci, none of which has been unequivocally shown to modify disease risk using conventional methodologies. Methods: Our group has created and continues to maintain a publicly available database ("AlzGene"; accessible at www. alzgene.org), which systematically collects and summarizes all genetic association studies in the field of AD published in peer-reviewed journals. One integral part of AlzGene are allele-based meta-analyses, which are performed for each polymorphism with genotype data available in at least four independent datasets. Results: Currently, AlzGene contains detailed summaries of nearly 1,200 genetic association studies investigating nearly 600 different loci. Nearly 30 of these loci contain at least one genetic variants showing nominally significant summary odds ratios upon meta-analysis of data from all published studies. The genetic effect sizes exerted by these loci are small, i.e. odds ratios in the order of 1.25. The presentation will provide a detailed overview of the genetic epidemiology of AD and highlight examples significant findings. A particular focus will be put on loci with consistent risk effects across independent datasets and with corresponding results across different study designs, e.g. ACE, CHRNB2, GAB2, and TF. Another emphasis will be laid on the emerging field of genome-wide association studies (GWAS), and their potential in resolving the complex genetic architechture underlying most forms of AD. This will also introduce recently generated GWAS findings from our group, suggesting the existence of a number of potential novel AD susceptibility genes in hitherto unrecognized chromosomal regions. Conclusions: Over the past 30 years, the field of AD genetics has substantially advanced our understanding of the pathogenetic forces driving neurodegeneration and dementia. As the field progresses with more powerful association testing strategies, additional loci with significant risk effects will emerge. AlzGene and related field synopses provide a powerful tool for continuously and quantitatively monitoring the progress within and across diseases, making results easily accessible to investigators of various different disciplines.