Background: DNA methylation is a widely studied epigenetic phenomenon; alterations in methylation patterns\ninfluence human phenotypes and risk of disease. As part of the Atherosclerosis Risk in Communities (ARIC) study,\nthe Illumina Infinium HumanMethylation450 (HM450) BeadChip was used to measure DNA methylation in\nperipheral blood obtained from ~3000 African American study participants. Over 480,000 cytosine-guanine (CpG)\ndinucleotide sites were surveyed on the HM450 BeadChip. To evaluate the impact of technical variation, 265\ntechnical replicates from 130 participants were included in the study.\nResults: For each CpG site, we calculated the intraclass correlation coefficient (ICC) to compare variation of\nmethylation levels within- and between-replicate pairs, ranging between 0 and 1. We modeled the distribution of\nICC as a mixture of censored or truncated normal and normal distributions using an EM algorithm. The CpG sites\nwere clustered into low- and high-reliability groups, according to the calculated posterior probabilities. We also\ndemonstrated the performance of this clustering when applied to a study of association between methylation levels\nand smoking status of individuals. For the CpG sites showing genome-wide significant association with smoking\nstatus, most (~96%) were seen from sites in the high reliability cluster.\nConclusions: We suggest that CpG sites with low ICC may be excluded from subsequent association analyses, or\nextra caution needs to be taken for associations at such sites
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