Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies

Friedrichs S, Manitz J, Burger P, Amos CI, Risch A, Chang-Claude J, Wichmann HE, Kneib T, Bickeboeller H, Hofner B (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Computational and Mathematical Methods in Medicine Taylor & Francis: STM, Behavioural Science and Public Health Titles / Taylor & Francis / Hindawi Publishing Corporation

Book Volume: 2017

DOI: 10.1155/2017/6742763

Abstract

The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.

Authors with CRIS profile

Benjamin Hofner Lehrstuhl für Biometrie und Epidemiologie

Involved external institutions

Georg-August-Universität Göttingen DE Germany (DE) Dartmouth College US United States (USA) (US) Universität Salzburg (Paris Lodron Universität Salzburg) AT Austria (AT) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE)

How to cite

APA:

Friedrichs, S., Manitz, J., Burger, P., Amos, C.I., Risch, A., Chang-Claude, J.,... Hofner, B. (2017). Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies. Computational and Mathematical Methods in Medicine, 2017. https://dx.doi.org/10.1155/2017/6742763

MLA:

Friedrichs, Stefanie, et al. "Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies." Computational and Mathematical Methods in Medicine 2017 (2017).

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