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Genet Epidemiol. 2009 Sep;33(6):479-87. doi: 10.1002/gepi.20400.

Replication of genetic associations as pseudoreplication due to shared genealogy.

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Department of Human Genetics, Center for Computational Medicine and Biology, and the Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109-2218, USA.


The genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype-phenotype associations using linkage disequilibrium between marker loci and disease-susceptibility loci can be considered as "pseudoreplicates" rather than true replicates. We examine the size of the pseudoreplication effect in association studies simulated from evolutionary models of the history of a population, evaluating the excess probability that both of a pair of studies detect a disease association compared to the probability expected under the assumption that the two studies are independent. Each of nine combinations of a demographic model and a penetrance model leads to a detectable pseudoreplication effect, suggesting that the degree of support that can be attributed to a replicated genetic association result is less than that which can be attributed to a replicated result in a context of true independence.

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