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.

journal_name

Genet Epidemiol

journal_title

Genetic epidemiology

authors

Rosenberg NA,Vanliere JM

doi

10.1002/gepi.20400

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

479-87

issue

6

eissn

0741-0395

issn

1098-2272

journal_volume

33

pub_type

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