Joint variable selection and network modeling for detecting eQTLs

Cao Xuan (), Ding Lili and Mersha Tesfaye B.
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Cao Xuan: Division of Statistics and Data Science, Department of Mathematical Sciences, University of Cincinnati, Cincinnati, OH 45221, USA
Ding Lili: Division of Biostatistics and Epidemiology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA
Mersha Tesfaye B.: Division of Asthma Research, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA

Statistical Applications in Genetics and Molecular Biology, 2020, vol. 19, issue 1, 15

Abstract: In this study, we conduct a comparison of three most recent statistical methods for joint variable selection and covariance estimation with application of detecting expression quantitative trait loci (eQTL) and gene network estimation, and introduce a new hierarchical Bayesian method to be included in the comparison. Unlike the traditional univariate regression approach in eQTL, all four methods correlate phenotypes and genotypes by multivariate regression models that incorporate the dependence information among phenotypes, and use Bayesian multiplicity adjustment to avoid multiple testing burdens raised by traditional multiple testing correction methods. We presented the performance of three methods (MSSL – Multivariate Spike and Slab Lasso, SSUR – Sparse Seemingly Unrelated Bayesian Regression, and OBFBF – Objective Bayes Fractional Bayes Factor), along with the proposed, JDAG (Joint estimation via a Gaussian Directed Acyclic Graph model) method through simulation experiments, and publicly available HapMap real data, taking asthma as an example. Compared with existing methods, JDAG identified networks with higher sensitivity and specificity under row-wise sparse settings. JDAG requires less execution in small-to-moderate dimensions, but is not currently applicable to high dimensional data. The eQTL analysis in asthma data showed a number of known gene regulations such as STARD3, IKZF3 and PGAP3, all reported in asthma studies. The code of the proposed method is freely available at GitHub (https://github.com/xuan-cao/Joint-estimation-for-eQTL).

Keywords: eQTL; join analysis; network modeling; variable selection (search for similar items in EconPapers)
Date: 2020
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DOI: 10.1515/sagmb-2019-0032

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