SNP association studies in Alzheimer's disease highlight problems for complex disease analysis

Genetic linkage and association analyses are two distinct approaches to und erstanding the genetic etiology of complex disease. Association analysis ha s become particularly popular in recent times, but the true utility of the strategy remains uncertain. To try to gain better insight into the relevant issues, we have used genetic association analysis to explore the etiology of alzheimer's disease. Our empirical findings supplement the theoretical d ebate, illustrating the general doubtfulness of previous positive findings and the limited ability of typical association studies based on candidate g enes to discern true medium-sized signals from false positives. Improvement s in genotyping technologies and increasing the number of SNPs tested, with out sophisticated allowance for all other issues, could simply lead to an u nmanageable overload of false-positive signals, themselves obscuring true d isease associations.