Evaluation of microarray-based DNA methylation measurement using technical replicates: the Atherosclerosis Risk In Communities (ARIC) Study

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  • Bose, Maitreyee
    • Other Affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA
  • Wu, Chong
    • Other Affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA
  • Pankow, James S
    • Other Affiliation: Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA
  • Demerath, Ellen W
    • Other Affiliation: Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA
  • Bressler, Jan
    • Other Affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
  • Fornage, Myriam
    • Other Affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
  • Grove, Megan L
    • Other Affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
  • Mosley, Thomas H
    • Other Affiliation: Department of Neurology and Department of Medicine, University of Mississippi, Jackson, MS 39216, USA
  • Hicks, Chindo
    • Other Affiliation: Department of Neurology and Department of Medicine, University of Mississippi, Jackson, MS 39216, USA
  • North, Kari
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Kao, Wen
    • Other Affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
  • Zhang, Yu
    • Other Affiliation: Department of Computer Science, Saint John’s University, Collegeville, MN 56321, USA
  • Boerwinkle, Eric
    • Other Affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
  • Guan, Weihua
    • Other Affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA
Abstract
  • Abstract Background DNA methylation is a widely studied epigenetic phenomenon; alterations in methylation patterns influence human phenotypes and risk of disease. As part of the Atherosclerosis Risk in Communities (ARIC) study, the Illumina Infinium HumanMethylation450 (HM450) BeadChip was used to measure DNA methylation in peripheral blood obtained from ~3000 African American study participants. Over 480,000 cytosine-guanine (CpG) dinucleotide sites were surveyed on the HM450 BeadChip. To evaluate the impact of technical variation, 265 technical replicates from 130 participants were included in the study. Results For each CpG site, we calculated the intraclass correlation coefficient (ICC) to compare variation of methylation levels within- and between-replicate pairs, ranging between 0 and 1. We modeled the distribution of ICC as a mixture of censored or truncated normal and normal distributions using an EM algorithm. The CpG sites were clustered into low- and high-reliability groups, according to the calculated posterior probabilities. We also demonstrated the performance of this clustering when applied to a study of association between methylation levels and smoking status of individuals. For the CpG sites showing genome-wide significant association with smoking status, most (~96%) were seen from sites in the high reliability cluster. Conclusions We suggest that CpG sites with low ICC may be excluded from subsequent association analyses, or extra caution needs to be taken for associations at such sites.
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  • Article
Rights statement
  • In Copyright
Rights holder
  • Maitreyee Bose et al.; licensee BioMed Central Ltd.
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Journal title
  • BMC Bioinformatics
Journal volume
  • 15
Journal issue
  • 1
Page start
  • 312
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1471-2105
Bibliographic citation
  • BMC Bioinformatics. 2014 Sep 19;15(1):312
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • August 26, 2015

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file details ICC values of all CpG sites. 2019-05-07 Public Download
file details Supplemental figures. 2019-05-07 Public Download