A systematic study of normalization methods for Infinium 450K methylation data using whole-genome bisulfite sequencing data

Wang, Ting; Guan, Weihua; Lin, Jerome; Boutaoui, Nadia; Canino, Glorisa; Luo, Jianhua; Celedón, Juan C.; Chen, Wei

doi:10.1080/15592294.2015.1057384

Cited by 75 publications

(65 citation statements)

References 22 publications

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“…Next, the methylation data were preprocessed by color balance adjustment, background correction and quantile-normalization with the lumi R package, and followed by Beta-Mixture Quantile (BMIQ) normalization with the wateRmelon package. This normalization strategy first quantile-normalized the intensities of methylation signals among all arrays, and then used BMIQ dilation to normalize the β-values within each array 16–18 .…”

Section: Methodsmentioning

confidence: 99%

An epigenome-wide association study of total serum IgE in Hispanic children

Chen

Wang

Pino-Yanes

et al. 2017

Journal of Allergy and Clinical Immunology

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Background Total immunoglobulin E (IgE) is a therapeutic target in allergic diseases. DNA methylation in white blood cells (WBCs) was associated with total IgE in an epigenome-wide association study (EWAS) of Caucasians. Whether DNA methylation of eosinophils explains those findings is insufficiently understood. Methods We tested for association between genome-wide DNA methylation in WBCs and total IgE in two studies of Hispanic children: the Puerto Rico Genetics of Asthma and Lifestyle Study (PR-GOAL, n = 306) and the Genes-environments and Admixture in Latino Americans (GALA II, n = 573). Whole-genome methylation of DNA from WBCs was measured using the Illumina Infinium HumanMethylation450 BeadChip. Total IgE was measured using the UniCAP 100 system. In PR-GOAL, WBC types (i.e. neutrophils, eosinophils, basophils, lymphocytes, and monocytes) in peripheral blood were measured using Coulter-Counter techniques. In GALA II, WBC types were imputed. Multivariable linear regression was used for the analysis of DNA methylation and total IgE, which was first conducted separately for each cohort, and then combining results from the two cohorts in a meta-analysis. Results CpG sites in multiple genes, including novel findings and results previously reported in Caucasians, were significantly associated with total IgE. However, adjustment for WBC types resulted in markedly fewer significant sites. Top findings from this adjusted meta-analysis were in genes ZFPM1 (P=1.5×10−12), ACOT7 (P=2.5×10−11), and MND1 (P=1.4×10−9). Conclusions In an EWAS adjusted for WBC types (including eosinophils), methylation changes in genes enriched in pathways relevant to asthma and immune responses were associated with total IgE among Hispanic children.

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Section: Methodsmentioning

confidence: 99%

An epigenome-wide association study of total serum IgE in Hispanic children

Chen

Wang

Pino-Yanes

et al. 2017

Journal of Allergy and Clinical Immunology

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“…Utilizing this as an actual DNA sequencing technology is hard to envision because the present method only examines one site in the duplex; however, probing methods to determine specific DNA sequences are still actively being pursued to overcome one limitation of full genome sequencing. 53,54 …”

Section: Resultsmentioning

confidence: 99%

Differentiation of G:C vs A:T and G:C vs G:mC Base Pairs in the Latch Zone of α-Hemolysin

et al. 2015

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The alpha-hemolysin (α-HL) nanopore can detect DNA strands under an electrophoretic force via many regions of the channel. Our laboratories previously demonstrated that trapping duplex DNA in the vestibule of wild-type α-HL under force could distinguish the presence of an abasic site compared to a G:C base pair positioned in the latch zone at the top of the vestibule. Herein, a series of duplexes were probed in the latch zone to establish if this region can detect more subtle features of base pairs beyond the complete absence of a base. The results of these studies demonstrate the most sensitive region of the latch can readily discriminate duplexes in which one G:C base pair is replaced by an A:T. Additional experiments determined that while neither 8-oxo-7,8-dihydroguanine nor 7-deazaguanine opposite C could be differentiated from a G:C base pair, in contrast, the epigenetic marker 5-methylcytosine, when present in both strands of the duplex, yielded new blocking currents when compared to strands with unmodified cytosine. The results are discussed with respect to experimental design for utilization of the latch zone of α-HL to probe specific regions of genomic samples.

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“…We consider it might due to the following issues: (1) Since there was no established methodology for calculating the power of genome-wide methylation study in twins, the sample size was still a problem. Reviews of twins for epigenetics suggested that "a relatively small number (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) of phenotypically discordant twin pairs had sufficient (>80%) power to detect epigenetic changes of 1.2-fold, where an effect size of 1.2-fold change was significantly greater than the null experimental variance threshold for the assay (1.15fold change)" 16,17 . Usually, the sample size of previous genome-wide methylation MZ twin study targeted on hypertension was about ten pairs.…”

Section: Discussionmentioning

confidence: 99%

“…(6) Methodology in methylation data processing needed to be further improved. So far, there was no consistent method for data standardization 20 . In this study, we used…”

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of DNA methylation in hypertension-discordant monozygotic twins

Gao

Cao

et al. 2020

Preprint

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Background: DNA methylation has great potential for identifying the aetiology of hypertension. The aim of this study was to explore the correlation between hypertension and DNA methylation using twins discordant for hypertension in China. Methods: In this study, 43 pairs of monozygotic twins discordant for hypertension (age 31.9-72.3 years; 67.4% male) from the Chinese National Twin Registry were recruited. Genome-wide DNA methylation was measured using the Illumina Human methylation EPIC Beadchip in whole-blood-derived DNA. Standardized questionnaires were used to collect twin data on the following variables: age, gender, socioeconomic level, lifestyle factors (including smoking, alcohol drinking, vegetable intake, and physical activity). Blood pressure, height, weight, and other anthropometric indicators were obtained by physical examination. Empirical Bayes paired moderated t-test was utilized to compare the methylation data within twin pairs. Results: Four suspected significant methylation sites, cg00950476, cg08041400, cg26733338, and cg08580087 were identified. All of these four sites locate on known loci, which were LINC01252, BDP1, SYT1, and ODZ4, respectively. The main function includes transcriptional regulation, learning and cognitive, neurodevelopment. The significant sites were further replicated among two different replication population, the first replication population contained 38 hypertension concordant monozygotic twin pairs and 38 non-hypertension concordant monozygotic twin pairs matched in age, sex, region, and birth order, and the second replication group included 21 MZ twin pairs discordant for hypertension . None of them, however, were significant. The methylation variation in the above sites may influence blood pressure, independent of genetic and early-life environmental factors. Conclusions: This study found four suspected methylation sites correlated with hypertension. However, all four sites failed the replication analysis. More hypertension-discordant monozygotic twin pairs are needed to replicate these findings in the future to explore the stability of the results.

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A systematic study of normalization methods for Infinium 450K methylation data using whole-genome bisulfite sequencing data

Cited by 75 publications

References 22 publications

An epigenome-wide association study of total serum IgE in Hispanic children

An epigenome-wide association study of total serum IgE in Hispanic children

Differentiation of G:C vs A:T and G:C vs G:mC Base Pairs in the Latch Zone of α-Hemolysin

Genome-wide analysis of DNA methylation in hypertension-discordant monozygotic twins

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