Robust regression based genome-wide multi-trait QTL analysis.

Md Jahangir Alam, Janardhan Mydam, Md Ripter Hossain, S M Shahinul Islam, Md Nurul Haque Mollah
Author Information
  1. Md Jahangir Alam: Bioinformatics Laboratory, Department of Statistics, University of Rajshahi, Rajshahi, 6205, Bangladesh. ORCID
  2. Janardhan Mydam: Division of Neonatology, Department of Pediatrics, John H. Stroger, Jr. Hospital of Cook County, 1969 Ogden Avenue, Chicago, IL, 60612, USA. ORCID
  3. Md Ripter Hossain: Bioinformatics Laboratory, Department of Statistics, University of Rajshahi, Rajshahi, 6205, Bangladesh.
  4. S M Shahinul Islam: Institute of Biological Science, University of Rajshahi, Rajshahi, 6205, Bangladesh.
  5. Md Nurul Haque Mollah: Bioinformatics Laboratory, Department of Statistics, University of Rajshahi, Rajshahi, 6205, Bangladesh. mollah.stat.bio@ru.ac.bd. ORCID

Abstract

In genome-wide quantitative trait locus (QTL) mapping studies, multiple quantitative traits are often measured along with the marker genotypes. Multi-trait QTL (MtQTL) analysis, which includes multiple quantitative traits together in a single model, is an efficient technique to increase the power of QTL identification. The two most widely used classical approaches for MtQTL mapping are Gaussian Mixture Model-based MtQTL (GMM-MtQTL) and Linear Regression Model-based MtQTL (LRM-MtQTL) analyses. There are two types of LRM-MtQTL approach known as least squares-based LRM-MtQTL (LS-LRM-MtQTL) and maximum likelihood-based LRM-MtQTL (ML-LRM-MtQTL). These three classical approaches are equivalent alternatives for QTL detection, but ML-LRM-MtQTL is computationally faster than GMM-MtQTL and LS-LRM-MtQTL. However, one major limitation common to all the above classical approaches is that they are very sensitive to outliers, which leads to misleading results. Therefore, in this study, we developed an LRM-based robust MtQTL approach, called LRM-RobMtQTL, for the backcross population based on the robust estimation of regression parameters by maximizing the β-likelihood function induced from the β-divergence with multivariate normal distribution. When β = 0, the proposed LRM-RobMtQTL method reduces to the classical ML-LRM-MtQTL approach. Simulation studies showed that both ML-LRM-MtQTL and LRM-RobMtQTL methods identified the same QTL positions in the absence of outliers. However, in the presence of outliers, only the proposed method was able to identify all the true QTL positions. Real data analysis results revealed that in the presence of outliers only our LRM-RobMtQTL approach can identify all the QTL positions as those identified in the absence of outliers by both methods. We conclude that our proposed LRM-RobMtQTL analysis approach outperforms the classical MtQTL analysis methods.

Keywords

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Grants

  1. HEQEP Sub-Project (CP-3603, W2, R3)/Rajshahi University and University Grant Commission (UGC), Govt. of Bangladesh

MeSH Term

Animals
Chromosome Mapping
Computer Simulation
Female
Genetics, Population
Genomics
Hordeum
Likelihood Functions
Mice, Inbred Strains
Quantitative Trait Loci
Mice

Word Cloud

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