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.
Original language | English (US) |
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Pages (from-to) | 479-487 |
Number of pages | 9 |
Journal | Genetic epidemiology |
Volume | 33 |
Issue number | 6 |
DOIs | |
State | Published - 2009 |
Externally published | Yes |
Keywords
- Coalescent
- Meta-analysis
- Population growth
ASJC Scopus subject areas
- Epidemiology
- Genetics(clinical)