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A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip improves data quality and performance in epigenome-wide association studies

Title: A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip improves data quality and performance in epigenome-wide association studies
Authors: Lehne, B
Drong, AW
Loh, M
Zhang, W
Scott, WR
Tan, S-T
Afzal, U
Scott, J
Jarvelin, M-R
Elliott, P
McCarthy, MI
Kooner, JS
Chambers, JC
Item 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.
Issue Date: 15-Feb-2015
Date of Acceptance: 28-Jan-2015
URI: http://hdl.handle.net/10044/1/28695
DOI: 10.1186/s13059-015-0600-x
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.
Sponsor/Funder: 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)
Funder's 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
Keywords: 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
Science & Technology
Life Sciences & Biomedicine
Biotechnology & Applied Microbiology
Genetics & Heredity
DNA METHYLATION
QUANTILE NORMALIZATION
SUBSET-QUANTILE
GENE-EXPRESSION
ARRAY
PIPELINE
CpG Islands
DNA Methylation
Epigenesis, Genetic
Epigenomics
Genome, Human
Genome-Wide Association Study
Humans
Oligonucleotide Array Sequence Analysis
Quantitative Trait Loci
Software
Humans
Oligonucleotide Array Sequence Analysis
DNA Methylation
Epigenesis, Genetic
CpG Islands
Quantitative Trait Loci
Genome, Human
Software
Genome-Wide Association Study
Epigenomics
05 Environmental Sciences
06 Biological Sciences
08 Information and Computing Sciences
Bioinformatics
Publication Status: Published
Article Number: ARTN 37
Appears in Collections:Institute of Clinical Sciences
Faculty of Medicine
School of Public Health