Dataset Information

MTG2: an efficient algorithm for multivariate linear mixed model analysis based on genomic information.

ABSTRACT:

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We have developed an algorithm for genetic analysis of complex traits using genome-wide SNPs in a linear mixed model framework. Compared to current standard REML software based on the mixed model equation, our method is substantially faster. The advantage is largest when there is only a single genetic covariance structure. The method is particularly useful for multivariate analysis, including multi-trait models and random regression models for studying reaction norms. We applied our proposed method to publicly available mice and human data and discuss the advantages and limitations.

Availability and implementation

MTG2 is available in https://sites.google.com/site/honglee0707/mtg2 CONTACT: hong.lee@une.edu.au

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Lee SH

PROVIDER: S-EPMC4848406 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

MTG2: an efficient algorithm for multivariate linear mixed model analysis based on genomic information.

Lee S H SH van der Werf J H J JH

Bioinformatics (Oxford, England) 20160110 9

<h4>Unlabelled</h4>We have developed an algorithm for genetic analysis of complex traits using genome-wide SNPs in a linear mixed model framework. Compared to current standard REML software based on the mixed model equation, our method is substantially faster. The advantage is largest when there is only a single genetic covariance structure. The method is particularly useful for multivariate analysis, including multi-trait models and random regression models for studying reaction norms. We appli ...[more]

PMID: 26755623

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Project description:BACKGROUND:Renal transplant patients are mandated to have continuous assessment of their kidney function over time to monitor disease progression determined by changes in blood urea nitrogen (BUN), serum creatinine (Cr), and estimated glomerular filtration rate (eGFR). Multivariate analysis of these outcomes that aims at identifying the differential factors that affect disease progression is of great clinical significance. Thus our study aims at demonstrating the application of different joint modeling approaches with random coefficients on a cohort of renal transplant patients and presenting a comparison of their performance through a pseudo-simulation study. The objective of this comparison is to identify the model with best performance and to determine whether accuracy compensates for complexity in the different multivariate joint models. METHODS AND RESULTS:We propose a novel application of multivariate Generalized Linear Mixed Models (mGLMM) to analyze multiple longitudinal kidney function outcomes collected over 3 years on a cohort of 110 renal transplantation patients. The correlated outcomes BUN, Cr, and eGFR and the effect of various covariates such patient's gender, age and race on these markers was determined holistically using different mGLMMs. The performance of the various mGLMMs that encompass shared random intercept (SHRI), shared random intercept and slope (SHRIS), separate random intercept (SPRI) and separate random intercept and slope (SPRIS) was assessed to identify the one that has the best fit and most accurate estimates. A bootstrap pseudo-simulation study was conducted to gauge the tradeoff between the complexity and accuracy of the models. Accuracy was determined using two measures; the mean of the differences between the estimates of the bootstrapped datasets and the true beta obtained from the application of each model on the renal dataset, and the mean of the square of these differences. The results showed that SPRI provided most accurate estimates and did not exhibit any computational or convergence problem. CONCLUSION:Higher accuracy was demonstrated when the level of complexity increased from shared random coefficient models to the separate random coefficient alternatives with SPRI showing to have the best fit and most accurate estimates.

Dataset Information

MTG2: an efficient algorithm for multivariate linear mixed model analysis based on genomic information.

Unlabelled

Availability and implementation

Supplementary information

Publications

MTG2: an efficient algorithm for multivariate linear mixed model analysis based on genomic information.

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