|
|
|
J.K. Pritchard, M. Stephens, N.A. Rosenberg and P. Donnelly, 2000. Association mapping in structured populations. Am J. Hum Genet. 67:170-181. The use in association studies of the forthcoming dense genome-wide collection of SNPs has been heralded as a potential breakthrough in studying the genetic basis of common complex disorders. A serious problem with association mapping is that population structure can lead to spurious associations between a candidate marker and a phenotype. One common solution has been to abandon case-control studies in favour of family-based tests of association, such as the TDT, but this comes at a considerable cost in the need to collect DNA from close relatives of affected individuals. In this article we describe a novel, statistically valid, method for case-control association studies in structured populations. Our method uses a set of unlinked genetic markers to infer details of population structure, and estimate the ancestry of sampled individuals, before using this information to test for associations within subpopulations. It provides power comparable with the TDT in many settings, and may substantially outperform it if there are conflicting associations in different subpopulations. Download PDF Download software
|
