Correcting for cell-type effects in DNA methylation studies: reference-based method outperforms latent variable approaches in empirical studies. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Hattab, Mohammad; Shabalin, Andrey; Clark, Shaunna; Zhao, Min; Kumar, Gaurav; Chan, Robin; Xie, Lin; Jansen, Rick; Han, Laura; Magnusson, Patrik; van Grootheest, Gerard; Hultman, Christina; Penninx, Brenda; Aberg, Karolina; van den Oord, Edwin
• Is Part Of: Genome biology. Volume 18:Issue 1(2017)
• Page Start: 1
• Page End: 3
• Publication Date: 2017-12
• Subjects: Genomes -- Periodicals; Biology -- Periodicals; Molecular biology -- Periodicals; 572.8633
• DOI: 10.1186/s13059-017-1148-8
• Languages: English
• ISSNs: 1474-760X

Abstract

Abstract Based on an extensive simulation study, McGregor and colleagues recently recommended the use of surrogate variable analysis (SVA) to control for the confounding effects of cell-type heterogeneity in DNA methylation association studies in scenarios where no cell-type proportions are available. As their recommendation was mainly based on simulated data, we sought to replicate findings in two large-scale empirical studies. In our empirical data, SVA did not fully correct for cell-type effects, its performance was somewhat unstable, and it carried a risk of missing true signals caused by removing variation that might be linked to actual disease processes. By contrast, a reference-based correction method performed well and did not show these limitations. A disadvantage of this approach is that if reference methylomes are not (publicly) available, they will need to be generated once for a small set of samples. However, given the notable risk we observed for cell-type confounding, we argue that, to avoid introducing false-positive findings into the literature, it could be well worth making this investment. Please see related Correspondence article:https://genomebiology.biomedcentral.com/articles/10/1186/s13059-017-1149-7 and related Research article:https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0935-y