Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: application to African-American populations.
We describe a novel method for analysis of marker genotype data from admixed populations, based on a hybrid of Bayesian and frequentist approaches in which the posterior distribution is generated by Markov chain simulation and score tests are obtained from the missing-data likelihood. We analysed data on unrelated individuals from eight African-American populations, genotyped at ten marker loci of which two (FY and AT3) are linked (22 cM apart). Linkage between these two loci was detected by testing for association of ancestry conditional on parental admixture. The strength of this association was consistent with European gene flow into the African-American population between five and nine generations ago. To mimic the mapping of an unknown gene in an 'affecteds- only' analysis, a binary trait was constructed from the genotype at the AT3 locus and a score test was shown to detect linkage of this 'trait' with the FY locus. Mis-specification of the ancestry-specific allele frequencies - the probabilities of each allelic state given the ancestry of the allele - was detected at three of the ten marker loci. The methods described here have wide application to the analysis of data from admixed populations, allowing the effects of linkage and population structure (variation of admixture between individuals) to be distinguished. With more markers and a more complex statistical model, genes underlying ethnic differences in disease risk could be mapped by this approach.
Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, UK. paul.mckeigue@Lshtm.ac.uk
P M
PM
McKeigue
J R
JR
Carpenter
E J
EJ
Parra
M D
MD
Shriver
D001499:Bayes Theorem; D044383:Black People / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D016013:Likelihood Functions; D001741:Black or African American