Replication of genetic associations as pseudoreplication due to shared genealogy

Noah A. Rosenberg, Jenna M. VanLiere

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)479-487
Number of pages9
JournalGenetic epidemiology
Volume33
Issue number6
DOIs
StatePublished - Sep 14 2009

Keywords

  • Coalescent
  • Meta-analysis
  • Population growth

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Replication of genetic associations as pseudoreplication due to shared genealogy'. Together they form a unique fingerprint.

  • Cite this