Journal
PATTERNS
Volume 1, Issue 2, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.patter.2020.100014
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Funding
- Medical Research Council [MR/P005918/1, G1002190]
- National Institute of Child Health and Human Development [HD077482]
- UK Economic and Social Research Council (ESRC) [ES/N000277/1]
- Biotechnology and Biological Sciences Research Council (BBSRC) [ES/N000277/1]
- MQ Fellows Award [MQ14F40]
- New Zealand Health Research Council
- New Zealand Ministry of Business, Innovation, and Employment
- National Institute on Aging [AG032282, AG049789]
- Jacobs Foundation
- Charles Lafitte Foundation Duke Faculty Seed Grant
- American Asthma Foundation
- British Academy Mid-Career Fellowship [MD\170005]
- North Carolina Biotechnology Center [2016-IDG-1013]
- ESRC [ES/N000277/1, ES/S012567/1] Funding Source: UKRI
- MRC [MR/M008924/1, G1002190, MR/R005176/1, MR/P005918/1] Funding Source: UKRI
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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 Methylation-EPIC 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 as a lesson for working with DNA methylation data, but the lessons are equally applicable to working with other data: as we advance toward generating increasingly greater volumes of data, failure to document reliability risks harming reproducibility.
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