MBD-seq - realities of a misunderstood method for high-quality methylome-wide association studies

ABSTRACT

The majority of methylome-wide association studies (MWAS) have been performed using commercially available array-based technologies such as the Infinium Human Methylation 450K and the Infinium MethylationEPIC arrays (Illumina). While these arrays offer a convenient and relatively robust assessment of the probed sites they only allow interrogation of 2-4% of all CpG sites in the human genome. Methyl-binding domain sequencing (MBD-seq) is an alternative approach for MWAS that provides near-complete coverage of the methylome at similar costs as the array-based technologies. However, despite publication of multiple positive evaluations, the use of MBD-seq for MWAS is often fiercely criticized. Here we discuss key features of the method and debunk misconceptions using empirical data. We conclude that MBD-seq represents an excellent approach for large-scale MWAS and that increased utilization is likely to result in more discoveries, advance biological knowledge, and expedite the clinical translation of methylome-wide research findings.

KEYWORDS:

• Epigenetics
• DNA methylation
• methyl-binding domain sequencing
• MBD-seq
• methylome-wide association study (MWAS)
• epigenome-wide association study (EWAS)
• RaMWAS software

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Institute of Mental Health [R01MH099110]; National Institute of Mental Health [R01MH109525]; National Institute of Mental Health [R01MH104576].