Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide variation of cytosine modifications between European and African populations and the implications for complex traits

ABSTRACT: Elucidating cytosine modification difference between human populations can enhance our understanding of ethnic specificity in complex traits such as disease predisposition and drug response. In this study, cytosine modification levels in 133 HapMap lymphoblastoid cell lines (LCLs) derived from individuals of European or African ancestry were profiled using the Illumina HumanMethylation450 BeadChip. Approximately 13% of the analyzed CpG sites showed differential modification between the two populations at false discovery rate (FDR) of 1%. CpG sites with greater modification levels in European descents were enriched in the proximal regulatory regions, while those greater in African descents were biased toward gene bodies. More than half of the detected population-specific cytosine modifications could be explained by genetic variation. A substantial proportion of local modification quantitative trait loci (mQTL) exhibited population-specific effects, suggesting that genetic epistasis and/or genotype × environment interaction could be common. Distinct inter-individual correlations were observed between gene expression and cytosine modifications in both proximal promoters and gene bodies, demonstrating a regulatory role of inter-individual variation in cytosine modification. Furthermore, a number of SNPs (single nucleotide polymorphisms) previously identified for complex traits with known racial disparities could be annotated as mQTLs for population-specific CpGs. Our findings revealed abundant population-specific cytosine modifications and the underlying genetic basis, as well as the relatively independent contribution of genetic and epigenetic variations to population differences in gene expression. 60 HapMap CEU and 73 HapMap YRI samples from Coriell Insitute were profiled for cytosine modification levels.

ORGANISM(S): Homo sapiens

SUBMITTER: Wei Zhang

PROVIDER: E-GEOD-39672 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genome-wide variation of cytosine modifications between European and African populations and the implications for complex traits.

Moen Erika L EL Zhang Xu X Mu Wenbo W Delaney Shannon M SM Wing Claudia C McQuade Jennifer J Myers Jamie J Godley Lucy A LA Dolan M Eileen ME Zhang Wei W

Genetics 20130621 4

Elucidating cytosine modification differences between human populations can enhance our understanding of ethnic specificity in complex traits. In this study, cytosine modification levels in 133 HapMap lymphoblastoid cell lines derived from individuals of European or African ancestry were profiled using the Illumina HumanMethylation450 BeadChip. Approximately 13% of the analyzed CpG sites showed differential modification between the two populations at a false discovery rate of 1%. The CpG sites w ...[more]

PMID: 23792949

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Project description:Treatment with recombinant human growth hormone (rhGH) has been consistently reported to induce transcriptional changes in various human tissues including peripheral blood. For other hormones it has been shown that the induction of such transcriptional effects is conferred or at least accompanied by DNA-methylation changes. To analyse effects of short term rhGH treatment on the DNA-methylome we investigated a total of 24 patients at baseline and after 4-day rhGH stimulation. We performed array-based DNA-methylation profiling of paired peripheral blood mononuclear cell samples followed by targeted validation using bisulfite pyrosequencing. Unsupervised analysis of DNA-methylation in this short-term treated cohort revealed clustering according to individuals rather than treatment. Supervised analysis identified 239 CpGs as significantly differentially methylated between baseline and rhGH-stimulated samples (p<0.0001, unadjusted paired t-test), which nevertheless did not retain significance after adjustment for multiple testing. An individualised evaluation strategy led to the identification of 2350 CpG and 3 CpH sites showing methylation differences of at least 10% in more than 2 of the 24 analysed sample pairs. To investigate the long term effects of rhGH treatment on the DNA-methylome, we analysed peripheral blood cells from an independent cohort of 36 rhGH treated children born small for gestational age (SGA) as compared to 18 untreated controls. Median treatment interval was 33 months. In line with the groupwise comparison in the short-term treated cohort no differentially methylated targets reached the level of significance in the long-term treated cohort. We identified marked intra-individual responses of DNA-methylation to short-term rhGH treatment. These responses seem to be predominately associated with immunologic functions and show considerable inter-individual heterogeneity. The latter is likely the cause for the lack of a rhGH induced homogeneous DNA-methylation signature after short- and long-term treatment, which nevertheless is well in line with generally assumed safety of rhGH treatment. Bisulfite converted DNA of PB from 36 SGA born children treated long-term with rhGH and 18 SGA born children with no rhGH treatment (controls) were hybridized to the Illumina Infinium HumanMethylation 450k Bead Chip.

Dataset Information

Genome-wide variation of cytosine modifications between European and African populations and the implications for complex traits

Publications

Genome-wide variation of cytosine modifications between European and African populations and the implications for complex traits.

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