An empirical Bayes approach for multiple tissue eQTL analysis

Biostatistics. 2018 Jul 1;19(3):391-406. doi: 10.1093/biostatistics/kxx048.

Abstract

Expression quantitative trait locus (eQTL) analyses identify genetic markers associated with the expression of a gene. Most up-to-date eQTL studies consider the connection between genetic variation and expression in a single tissue. Multi-tissue analyses have the potential to improve findings in a single tissue, and elucidate the genotypic basis of differences between tissues. In this article, we develop a hierarchical Bayesian model (MT-eQTL) for multi-tissue eQTL analysis. MT-eQTL explicitly captures patterns of variation in the presence or absence of eQTL, as well as the heterogeneity of effect sizes across tissues. We devise an efficient Expectation-Maximization (EM) algorithm for model fitting. Inferences concerning eQTL detection and the configuration of eQTL across tissues are derived from the adaptive thresholding of local false discovery rates, and maximum a posteriori estimation, respectively. We also provide theoretical justification of the adaptive procedure. We investigate the MT-eQTL model through an extensive analysis of a 9-tissue data set from the GTEx initiative.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bayes Theorem
  • Biostatistics / methods*
  • Gene Expression*
  • Genomics / methods*
  • Genotyping Techniques / methods*
  • Humans
  • Models, Statistical*
  • Quantitative Trait Loci*