Local phylogeny mapping of quantitative traits: Higher accuracy and better ranking than single-marker association in genomewide scans

Abstract

We present a new method, termed QBlossoc, for linkage disequilibrium (LD) mapping of genetic variants underlying a quantitative trait. The method uses principles similar to a previously published method, Blossoc, for LD mapping of case/control studies. The method builds local genealogies along the genome and looks for a significant clustering of quantitative trait values in these trees. We analyze its efficiency in terms of localization and ranking of true positives among a large number of negatives and compare the results with single-marker approaches. Simulation results of markers at densities comparable to contemporary genotype chips show that QBlossoc is more accurate in localization of true positives as expected since it uses the additional information of LD between markers simultaneously. More importantly, however, for genomewide surveys, QBlossoc places regions with true positives higher on a ranked list than single-marker approaches, again suggesting that a true signal displays itself more strongly in a set of adjacent markers than a spurious (false) signal. The method is both memory and central processing unit (CPU) efficient. It has been tested on a real data set of height data for 5000 individuals measured at ∼317,000 markers and completed analysis within 5 CPU days. Copyright © 2009 by the Genetics Society of America.