A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip improves data quality and performance in epigenome-wide association studies
Author(s)
Type
Journal Article
Abstract
DNA methylation plays a fundamental role in the regulation of the genome, but the optimal strategy for analysis of
genome-wide DNA methylation data remains to be determined. We developed a comprehensive analysis pipeline
for epigenome-wide association studies (EWAS) using the Illumina Infinium HumanMethylation450 BeadChip, based
on 2,687 individuals, with 36 samples measured in duplicate. We propose new approaches to quality control, data
normalisation and batch correction through control-probe adjustment and establish a null hypothesis for EWAS
using permutation testing. Our analysis pipeline outperforms existing approaches, enabling accurate identification
of methylation quantitative trait loci for hypothesis driven follow-up experiments.
genome-wide DNA methylation data remains to be determined. We developed a comprehensive analysis pipeline
for epigenome-wide association studies (EWAS) using the Illumina Infinium HumanMethylation450 BeadChip, based
on 2,687 individuals, with 36 samples measured in duplicate. We propose new approaches to quality control, data
normalisation and batch correction through control-probe adjustment and establish a null hypothesis for EWAS
using permutation testing. Our analysis pipeline outperforms existing approaches, enabling accurate identification
of methylation quantitative trait loci for hypothesis driven follow-up experiments.
Date Issued
2015-02-15
Date Acceptance
2015-01-28
Citation
Genome Biology, 2015, 16 (1)
ISSN
1474-760X
Publisher
BioMed Central
Journal / Book Title
Genome Biology
Volume
16
Issue
1
Copyright Statement
© 2015 Lehne et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.
Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.
License URL
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
Action on Hearing Loss
Wellcome Trust
British Heart Foundation
Medical Research Council (MRC)
Medical Research Council (MRC)
Grant Number
G0700931
G0601966
MR/L01341X/1
NF-SI-0611-10136
RDC01 79560
RTJ6219303-1
G51_Chambers
084723/Z/08/Z
SP/04/02
G0801056B
MR/K002414/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Biotechnology & Applied Microbiology
Genetics & Heredity
METHYLATION ARRAY DATA
DNA METHYLATION
QUANTILE NORMALIZATION
PANCREATIC-ISLETS
PERIPHERAL-BLOOD
SUBSET-QUANTILE
GENE-EXPRESSION
MICROARRAY
PIPELINE
CANCER
Publication Status
Published
Article Number
ARTN 37