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There is no doubt that candidate gene association studies can play a useful part in detecting genetic variations contributing to complex diseases such as Alzheimer's disease. 1 Yasudaet al present a paper in this issue (pp 772-6 ) in which they use this approach to test for an association between the 1-1 genotype of an intronic polymorphism in the presenilin 1 (PS-1) gene and Alzheimer's disease, originally reported by Wragget al . 2 Although Yasudaet al did not replicate this effect in their sample of 217 patients and matched controls, they did find a significant excess of the 1-1 genotype in a meta-analysis of published studies.
Several reasons could account for the...