Application of two machine learning algorithms to genetic association studies in the presence of covariates

Bareng A.S. Nonyane, Andrea S. Foulkes

Research output: Contribution to journalArticlepeer-review


Background: Population-based investigations aimed at uncovering genotype-trait associations often involve high-dimensional genetic polymorphism data as well as information on multiple environmental and clinical parameters. Machine learning (ML) algorithms offer a straightforward analytic approach for selecting subsets of these inputs that are most predictive of a pre-defined trait. The performance of these algorithms, however, in the presence of covariates is not well characterized. Methods and Results: In this manuscript, we investigate two approaches: Random Forests (RFs) and Multivariate Adaptive Regression Splines (MARS). Through multiple simulation studies, the performance under several underlying models is evaluated. An application to a cohort of HIV-1 infected individuals receiving anti-retroviral therapies is also provided. Conclusion: Consistent with more traditional regression modeling theory, our findings highlight the importance of considering the nature of underlying gene-covariate-trait relationships before applying ML algorithms, particularly when there is potential confounding or effect mediation.

Original languageEnglish (US)
Article number71
JournalBMC genetics
StatePublished - Nov 14 2008
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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