MethylPCA: a toolkit to control for confounders in methylome-wide association studies

BMC Bioinformatics

Wenan Chen¹  Guimin Gao¹  Srilaxmi Nerella⁴  Christina M Hultman³  Patrik KE Magnusson³  Patrick F Sullivan²  Karolina A Aberg⁴  Edwin JCG van den Oord⁴ 

[1] Department of Biostatistics, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA

[2] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

[3] Swedish Schizophrenia Consortium, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

[4] Center for Biomarker Research and Personalized Medicine, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA

关键词: MBD-seq;    Association test;    Eigen-decomposition;    Methylome-wide association studies;    Principal component analysis;   

Others  :  1087960
DOI  :  10.1186/1471-2105-14-74

 received in 2012-10-10, accepted in 2013-02-20,  发布年份 2013

【 摘 要 】

Background

In methylome-wide association studies (MWAS) there are many possible differences between cases and controls (e.g. related to life style, diet, and medication use) that may affect the methylome and produce false positive findings. An effective approach to control for these confounders is to first capture the major sources of variation in the methylation data and then regress out these components in the association analyses. This approach is, however, computationally very challenging due to the extremely large number of methylation sites in the human genome.

Result

We introduce MethylPCA that is specifically designed to control for potential confounders in studies where the number of methylation sites is extremely large. MethylPCA offers a complete and flexible data analysis including 1) an adaptive method that performs data reduction prior to PCA by empirically combining methylation data of neighboring sites, 2) an efficient algorithm that performs a principal component analysis (PCA) on the ultra high-dimensional data matrix, and 3) association tests. To accomplish this MethylPCA allows for parallel execution of tasks, uses C++ for CPU and I/O intensive calculations, and stores intermediate results to avoid computing the same statistics multiple times or keeping results in memory. Through simulations and an analysis of a real whole methylome MBD-seq study of 1,500 subjects we show that MethylPCA effectively controls for potential confounders.

Conclusions

MethylPCA provides users a convenient tool to perform MWAS. The software effectively handles the challenge in memory and speed to perform tasks that would be impossible to accomplish using existing software when millions of sites are interrogated with the sample sizes required for MWAS.

【 授权许可】

   
2013 Chen et al; licensee BioMed Central Ltd.

【 图 表 】

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