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Keywords:

  • inverted regression;
  • genomic control;
  • MultiPhen;
  • pleiotropy;
  • proportional odds model;
  • population structure;
  • principal component analysis;
  • variance inflation factor

ABSTRACT

Testing association between a genetic marker and multiple-dependent traits is a challenging task when both binary and quantitative traits are involved. The inverted regression model is a convenient method, in which the traits are treated as predictors although the genetic marker is an ordinal response. It is known that population stratification (PS) often affects population-based association studies. However, how it would affect the inverted regression for pleiotropic association, especially with the mixed types of traits (binary and quantitative), is not examined and the performance of existing methods to correct for PS using the inverted regression analysis is unknown. In this paper, we focus on the methods based on genomic control and principal component analysis, and investigate type I error of pleiotropic association using the inverted regression model in the presence of PS with allele frequencies and the distributions (or disease prevalences) of multiple traits varying across the subpopulations. We focus on common alleles but simulation results for a rare variant are also reported. An application to the HapMap data is used for illustration.