Distinguishing Close Linkage from Pleiotropy in Multiparental Populations

• Activity Number: 246 - New Mothods for Biomedical and Genetics Data
• Type: Contributed
• Date/Time: Monday, July 30, 2018 : 2:00 PM to 3:50 PM
• Sponsor: Section on Statistics in Genomics and Genetics
• Author(s): Frederick Boehm* and Mark Keller and Alan Attie and Brian Yandell and Karl Broman
• Companies: University of Wisconsin - Madison and University of Wisconsin-Madison and University of Wisconsin-Madison and University of Wisconsin-Madison and University of Wisconsin-Madison
• Keywords: multi-parental populations; diversity outbred mice; quantitative trait locus; pleiotropy; systems genetics

Abstract

Multiparental populations, such as the Diversity Outbred (DO) mouse population, are a new resource for systems genetics studies. Distinguishing close linkage of distinct quantitative trait loci from one pleiotropic locus that associates with multiple traits has implications in biomedical research, plant and animal breeding, and other genetics applications. We develop a likelihood ratio test for the alternative hypothesis of close linkage of two loci against the null hypothesis of pleiotropy for a pair of traits that map to a single genomic region. Unlike previous tests of these competing hypotheses, our test incorporates polygenic random effects to account for complex patterns of relatedness among subjects. Additionally, our test accommodates more than two founder alleles. We use a parametric bootstrap-based method to determine statistical significance. To demonstrate its practical utility, we apply our test to a study of 400 DO mice. We share our methods in a freely available software package (https://github.com/fboehm/qtl2pleio) for the R statistical computing environment.