GeneralizedRegionalAdmixtureMapping(RAM)and.pptVIP

Generalized Regional Admixture Mapping (RAM) and Structured Association Testing (SAT) David T. Redden, Associate Professor, Department of Biostatistics, University of Alabama at Birmingham Acknowledgements Jose Fernandez Jasmin Divers Kelly Vaughan Solomon Musani Hemant Tiwari Miguel Padilla Michael B. Miller The problem and the promise Admixture, the event of two or more populations with different allele frequencies intermating, creates offspring with linkage disequilibrium that spans a greater distance than in a panmictic population. The problem and the promise This admixture process can, under some circumstances, create disequilibrium between pairs of unlinked loci and thus create confounding (spurious associations, inflated false positive results) in genetic association studies between trait and marker. The problem and the promise The classic example is found in Knowler et al (1988). They reported an association between an HLA haplotype and diabetes for Pima Indians. When the analysis was repeated stratifying subjects by amount of European ancestry, the observed association between HLA haplotype and diabetes was not present. The Problem Structured Association Tests In response to this problem, many authors have proposed a collection of methods we will collectively call SAT. The promise Regional admixture mapping (RAM) methods use genome wide ancestry and region specific admixture estimates to identify specific regions of the genome potentially harboring loci influencing the trait. The promise (Illustrated) Hypothetical Segment of an Admixed Individual. Objective of the Paper To extend both Regional Admixture Mapping (RAM) and Structured Association Tests (SAT) into a regression modeling framework. This would allow for tests of dominance, allow for either continuous or dichotomous outcomes, and allow for inclusion of covariates. Regional Admixture Mapping Using a sample of admixed individuals, estimate each individual’s ancestry as well as estimate t