Behavior of QQ-plots and genomic control in studies of gene-environment interaction

PLoS One. 2011 May 12;6(5):e19416. doi: 10.1371/journal.pone.0019416.


Genome-wide association studies of gene-environment interaction (GxE GWAS) are becoming popular. As with main effects GWAS, quantile-quantile plots (QQ-plots) and Genomic Control are being used to assess and correct for population substructure. However, in G x E work these approaches can be seriously misleading, as we illustrate; QQ-plots may give strong indications of substructure when absolutely none is present. Using simulation and theory, we show how and why spurious QQ-plot inflation occurs in G x E GWAS, and how this differs from main-effects analyses. We also explain how simple adjustments to standard regression-based methods used in G x E GWAS can alleviate this problem.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Environment*
  • Genome-Wide Association Study
  • Genomics*
  • Humans