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Problems and Solutions in the Genetic Analysis of Late-Onset Alzheimer’s Disease

The identification of the apolipoprotein E gene as a risk factor for late-onset Alzheimer’s disease was a spectacularly successful application of genetic analysis to a complex trait, and it led to the hope and expectation that other risk loci for the disease would soon be forthcoming. Twelve years later, despite a huge amount of work, no other loci have been identified. In this article, we discuss the complexity of the problem and the pitfalls in the analytical methods that have been used and how we are approaching this problem.