title: Replication of genetic associations as pseudoreplication due to shared genealogy.
abstract: 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.
authors.affiliation: Department of Human Genetics, Center for Computational Medicine and Biology, and the Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109-2218, USA. rnoah@umich.edu
authors.forename: Noah A
authors.initials: NA
authors.lastname: Rosenberg
authors.forename: Jenna M
authors.initials: JM
authors.lastname: Vanliere
mesh_terms: D004247:DNA / Q000235:genetics*; D004261:DNA Replication; D004171:Diploidy; D019143:Evolution, Molecular; D005789:Genealogy and Heraldry; D005819:Genetic Markers; D006801:Humans; D008957:Models, Genetic; D011995:Recombination, Genetic
chemical_list: D005819:Genetic Markers; D004247:DNA