Recommendations for the design and analysis of epigenome-wide association studies

Karin B. Michels, Alexandra M. Binder, Sarah Dedeurwaerder, Charles B. Epstein, John M. Greally, Ivo Gut, E. Andres Houseman, Benedetta Izzi, Karl T. Kelsey, Alexander Meissner, Aleksandar Milosavljevic, Kimberly D. Siegmund, Christoph Bock, Rafael A. Irizarry

Research output: Contribution to journalArticle

189 Citations (Scopus)

Abstract

Epigenome-wide association studies (EWAS) hold promise for the detection of new regulatory mechanisms that may be susceptible to modification by environmental and lifestyle factors affecting susceptibility to disease. Epigenome-wide screening methods cover an increasing number of CpG sites, but the complexity of the data poses a challenge to separating robust signals from noise. Appropriate study design, a detailed a priori analysis plan and validation of results are essential to minimize the danger of false positive results and contribute to a unified approach. Epigenome-wide mapping studies in homogenous cell populations will inform our understanding of normal variation in the methylome that is not associated with disease or aging. Here we review concepts for conducting a stringent and powerful EWAS, including the choice of analyzed tissue, sources of variability and systematic biases, outline analytical solutions to EWAS-specific problems and highlight caveats in interpretation of data generated from samples with cellular heterogeneity.

Original languageEnglish (US)
Pages (from-to)949-955
Number of pages7
JournalNature Methods
Volume10
Issue number10
DOIs
StatePublished - Oct 2013

Fingerprint

Disease Susceptibility
Life Style
Population
Screening
Aging of materials
Cells
Tissue

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology
  • Biochemistry
  • Cell Biology

Cite this

Michels, K. B., Binder, A. M., Dedeurwaerder, S., Epstein, C. B., Greally, J. M., Gut, I., ... Irizarry, R. A. (2013). Recommendations for the design and analysis of epigenome-wide association studies. Nature Methods, 10(10), 949-955. https://doi.org/10.1038/nmeth.2632

Recommendations for the design and analysis of epigenome-wide association studies. / Michels, Karin B.; Binder, Alexandra M.; Dedeurwaerder, Sarah; Epstein, Charles B.; Greally, John M.; Gut, Ivo; Houseman, E. Andres; Izzi, Benedetta; Kelsey, Karl T.; Meissner, Alexander; Milosavljevic, Aleksandar; Siegmund, Kimberly D.; Bock, Christoph; Irizarry, Rafael A.

In: Nature Methods, Vol. 10, No. 10, 10.2013, p. 949-955.

Research output: Contribution to journalArticle

Michels, KB, Binder, AM, Dedeurwaerder, S, Epstein, CB, Greally, JM, Gut, I, Houseman, EA, Izzi, B, Kelsey, KT, Meissner, A, Milosavljevic, A, Siegmund, KD, Bock, C & Irizarry, RA 2013, 'Recommendations for the design and analysis of epigenome-wide association studies', Nature Methods, vol. 10, no. 10, pp. 949-955. https://doi.org/10.1038/nmeth.2632
Michels KB, Binder AM, Dedeurwaerder S, Epstein CB, Greally JM, Gut I et al. Recommendations for the design and analysis of epigenome-wide association studies. Nature Methods. 2013 Oct;10(10):949-955. https://doi.org/10.1038/nmeth.2632
Michels, Karin B. ; Binder, Alexandra M. ; Dedeurwaerder, Sarah ; Epstein, Charles B. ; Greally, John M. ; Gut, Ivo ; Houseman, E. Andres ; Izzi, Benedetta ; Kelsey, Karl T. ; Meissner, Alexander ; Milosavljevic, Aleksandar ; Siegmund, Kimberly D. ; Bock, Christoph ; Irizarry, Rafael A. / Recommendations for the design and analysis of epigenome-wide association studies. In: Nature Methods. 2013 ; Vol. 10, No. 10. pp. 949-955.
@article{1446ec838e904d049955edf1ee42eaa8,
title = "Recommendations for the design and analysis of epigenome-wide association studies",
abstract = "Epigenome-wide association studies (EWAS) hold promise for the detection of new regulatory mechanisms that may be susceptible to modification by environmental and lifestyle factors affecting susceptibility to disease. Epigenome-wide screening methods cover an increasing number of CpG sites, but the complexity of the data poses a challenge to separating robust signals from noise. Appropriate study design, a detailed a priori analysis plan and validation of results are essential to minimize the danger of false positive results and contribute to a unified approach. Epigenome-wide mapping studies in homogenous cell populations will inform our understanding of normal variation in the methylome that is not associated with disease or aging. Here we review concepts for conducting a stringent and powerful EWAS, including the choice of analyzed tissue, sources of variability and systematic biases, outline analytical solutions to EWAS-specific problems and highlight caveats in interpretation of data generated from samples with cellular heterogeneity.",
author = "Michels, {Karin B.} and Binder, {Alexandra M.} and Sarah Dedeurwaerder and Epstein, {Charles B.} and Greally, {John M.} and Ivo Gut and Houseman, {E. Andres} and Benedetta Izzi and Kelsey, {Karl T.} and Alexander Meissner and Aleksandar Milosavljevic and Siegmund, {Kimberly D.} and Christoph Bock and Irizarry, {Rafael A.}",
year = "2013",
month = "10",
doi = "10.1038/nmeth.2632",
language = "English (US)",
volume = "10",
pages = "949--955",
journal = "Nature Methods",
issn = "1548-7091",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Recommendations for the design and analysis of epigenome-wide association studies

AU - Michels, Karin B.

AU - Binder, Alexandra M.

AU - Dedeurwaerder, Sarah

AU - Epstein, Charles B.

AU - Greally, John M.

AU - Gut, Ivo

AU - Houseman, E. Andres

AU - Izzi, Benedetta

AU - Kelsey, Karl T.

AU - Meissner, Alexander

AU - Milosavljevic, Aleksandar

AU - Siegmund, Kimberly D.

AU - Bock, Christoph

AU - Irizarry, Rafael A.

PY - 2013/10

Y1 - 2013/10

N2 - Epigenome-wide association studies (EWAS) hold promise for the detection of new regulatory mechanisms that may be susceptible to modification by environmental and lifestyle factors affecting susceptibility to disease. Epigenome-wide screening methods cover an increasing number of CpG sites, but the complexity of the data poses a challenge to separating robust signals from noise. Appropriate study design, a detailed a priori analysis plan and validation of results are essential to minimize the danger of false positive results and contribute to a unified approach. Epigenome-wide mapping studies in homogenous cell populations will inform our understanding of normal variation in the methylome that is not associated with disease or aging. Here we review concepts for conducting a stringent and powerful EWAS, including the choice of analyzed tissue, sources of variability and systematic biases, outline analytical solutions to EWAS-specific problems and highlight caveats in interpretation of data generated from samples with cellular heterogeneity.

AB - Epigenome-wide association studies (EWAS) hold promise for the detection of new regulatory mechanisms that may be susceptible to modification by environmental and lifestyle factors affecting susceptibility to disease. Epigenome-wide screening methods cover an increasing number of CpG sites, but the complexity of the data poses a challenge to separating robust signals from noise. Appropriate study design, a detailed a priori analysis plan and validation of results are essential to minimize the danger of false positive results and contribute to a unified approach. Epigenome-wide mapping studies in homogenous cell populations will inform our understanding of normal variation in the methylome that is not associated with disease or aging. Here we review concepts for conducting a stringent and powerful EWAS, including the choice of analyzed tissue, sources of variability and systematic biases, outline analytical solutions to EWAS-specific problems and highlight caveats in interpretation of data generated from samples with cellular heterogeneity.

UR - http://www.scopus.com/inward/record.url?scp=84884828422&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884828422&partnerID=8YFLogxK

U2 - 10.1038/nmeth.2632

DO - 10.1038/nmeth.2632

M3 - Article

C2 - 24076989

AN - SCOPUS:84884828422

VL - 10

SP - 949

EP - 955

JO - Nature Methods

JF - Nature Methods

SN - 1548-7091

IS - 10

ER -