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Powerful tests for multi-marker association analysis using ensemble learning

Badri Padhukasahasram, Chandan K. Reddy, L. Keoki Williams
doi: https://doi.org/10.1101/005405
Badri Padhukasahasram
*Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Michigan, USA, 48202
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Chandan K. Reddy
§Department of Computer Science, Wayne State University, Detroit, Michigan, USA, 48202
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L. Keoki Williams
*Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Michigan, USA, 48202
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ABSTRACT

Multi-marker approaches are currently gaining a lot of interest in genome wide association studies and can enhance power to detect new associations under certain conditions. Gene and pathway based association tests are increasingly being viewed as useful complements to the more widely used single marker association analysis which have successfully uncovered numerous disease variants. A major drawback of single-marker based methods is that they do not consider pairwise and higher-order interactions between genetic variants. Here, we describe novel tests for multi-marker association analyses that are based on phenotype predictions obtained from machine learning algorithms. Instead of utilizing only a linear or logistic regression model, we propose the use of ensembles of diverse machine learning algorithms for constructing such association tests. As the true mathematical relationship between a phenotype and any group of genetic and clinical variables is unknown in advance and may be complex, such a strategy gives us a general and flexible framework to approximate this relationship across different sets of SNPs. We show how phenotype prediction obtained from ensemble learning algorithms can be used for constructing tests for the joint association of multiple variants. We first apply our method to simulated datasets to demonstrate its power and correctness. Then, we apply our method to previously studied asthma-related genes in two independent asthma cohorts to conduct association tests.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 13, 2014.
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Powerful tests for multi-marker association analysis using ensemble learning
Badri Padhukasahasram, Chandan K. Reddy, L. Keoki Williams
bioRxiv 005405; doi: https://doi.org/10.1101/005405
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Powerful tests for multi-marker association analysis using ensemble learning
Badri Padhukasahasram, Chandan K. Reddy, L. Keoki Williams
bioRxiv 005405; doi: https://doi.org/10.1101/005405

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