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- Title
Significance analysis and statistical dissection of variably methylated regions.
- Authors
Jaffe, Andrew E.; Feinberg, Andrew P.; Irizarry, Rafael A.; Leek, Jeffrey T.
- Abstract
It has recently been proposed that variation in DNA methylation at specific genomic locations may play an important role in the development of complex diseases such as cancer. Here, we develop 1- and 2-group multiple testing procedures for identifying and quantifying regions of DNA methylation variability. Our method is the first genome-wide statistical significance calculation for increased or differential variability, as opposed to the traditional approach of testing for mean changes. We apply these procedures to genome-wide methylation data obtained from biological and technical replicates and provide the first statistical proof that variably methylated regions exist and are due to interindividual variation. We also show that differentially variable regions in colon tumor and normal tissue show enrichment of genes regulating gene expression, cell morphogenesis, and development, supporting a biological role for DNA methylation variability in cancer.
- Subjects
METHYLATION; DNA; GENETICS of colon cancer; GENETIC regulation; DATA analysis; MORPHOGENESIS; BIOMETRY
- Publication
Biostatistics, 2012, Vol 13, Issue 1, p166
- ISSN
1465-4644
- Publication type
Article
- DOI
10.1093/biostatistics/kxr013