Patterns of reliability: Assessing the reproducibility and integrity of DNA methylation measurement

TY - JOUR

T1 - Patterns of reliability: Assessing the reproducibility and integrity of DNA methylation measurement

AU - Sugden, Karen

AU - Hannon, Eilis

AU - Arseneault, Louise

AU - Belsky, Daniel W.

AU - Corcoran, David L.

AU - Fisher, Helen

AU - Houts, Renate M

AU - Kandaswamy, Radhika

AU - Moffitt, Terrie

AU - Poulton, Richie

AU - Prinz, Joseph A

AU - Rasmussen, Line Jee Hartmann

AU - Williams, Benjamin

AU - Wong, Chloe

AU - Mill, Jonathan

AU - Caspi, Avshalom

PY - 2020/5/8

Y1 - 2020/5/8

N2 - DNA methylation plays an important role in both normal human development and risk of disease. The most utilized method of assessing DNA methylation uses BeadChips, generating an epigenome-wide ‘snapshot’ of >450,000 observations (probe measurements) per assay. However, the reliability of each of these measurements is not equal, and little consideration is paid to consequences for research. We correlated repeat measurements of the same DNA samples using the Illumina HumanMethylation450K and the Infinium MethylationEPIC BeadChips in 350 blood-DNA samples. Probes that were reliably measured were more heritable, and showed consistent associations with environmental exposures, gene expression, and greater cross-tissue concordance. Unreliable probes were less replicable and generated an unknown volume of false negatives. This serves a lesson for working with DNA methylation data, but the lessons are equally applicable to working with other data: as we advance towards generating increasingly greater volumes of data, failure to document reliability risks harming reproducibility.

AB - DNA methylation plays an important role in both normal human development and risk of disease. The most utilized method of assessing DNA methylation uses BeadChips, generating an epigenome-wide ‘snapshot’ of >450,000 observations (probe measurements) per assay. However, the reliability of each of these measurements is not equal, and little consideration is paid to consequences for research. We correlated repeat measurements of the same DNA samples using the Illumina HumanMethylation450K and the Infinium MethylationEPIC BeadChips in 350 blood-DNA samples. Probes that were reliably measured were more heritable, and showed consistent associations with environmental exposures, gene expression, and greater cross-tissue concordance. Unreliable probes were less replicable and generated an unknown volume of false negatives. This serves a lesson for working with DNA methylation data, but the lessons are equally applicable to working with other data: as we advance towards generating increasingly greater volumes of data, failure to document reliability risks harming reproducibility.

KW - DNA Methylation

KW - Reproducibility of Results

KW - Reliability

KW - Epigenesis

KW - Genetic

KW - Epigenomics

U2 - 10.1016/j.patter.2020.100014

DO - 10.1016/j.patter.2020.100014

M3 - Article

SP - 100014

JO - Patterns

JF - Patterns

ER -