Dataset Information

DNA methylome analysis of human peripheral blood samples in cancer discordant monozygotic twin-pairs

ABSTRACT: Genome wide DNA methylation profiling with the HumanMethylation450 BeadChip (450k) of peripheral blood samples of 46 adult female monozygotic twin-pairs obtained at the same time point. Samples included 41 healthy females (not diagnosed with cancer to date) paired with their co-twin diagnosed with cancer within a 5 year window around the time of sampling as well as 5 extra pairs with a co-twin diagnosed with cancer within 11 to 5 years prior to blood sampling.

ORGANISM(S): Homo sapiens

PROVIDER: GSE89093 | GEO | 2016/10/25

SECONDARY ACCESSION(S): PRJNA350276

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background Subcutaneous adipose tissue (SAT) undergoes major changes in obesity, but little is known about the whole-genome scale patterns of these changes or about their variation between different obesity subgroups. We sought to compare how transcriptomics profiles in SAT differ between monozygotic (MZ) co-twins who are discordant for body mass index (BMI), whether the profiles vary between twin pairs and whether the variation can be linked to clinical characteristics. Methods We analyzed the transcriptomics (Affymetrix U133 Plus 2.0) patterns of SAT in young MZ twin pairs (n =26, intrapair difference in BMI>3 kg/m2, aged 23-36), from 10 birth cohorts of adult Finnish twins. The clinical data included measurements of body composition, insulin resistance, lipids, and adipokines. Results We found 2108 genes differentially expressed (FDR<0.05) in SAT of the BMI-discordant pairs. Pathway analyses of these genes revealed a significant downregulation of mitochondrial oxidative pathways (p<0.05) and upregulation of inflammation pathways (p<0.05). Hierarchical clustering of heavy/lean twin ratios, representing effects of acquired obesity in the transcriptomics data, revealed three sub-groups with different molecular profiles (FDR<0.05). Analyses comparing these sub-groups showed that, in the heavy co-twins, downregulation of the mitochondrial pathways, especially that of branched chain amino acid (BCAA) degradation was more evident in two last clusters while and upregulation of the inflammatory response was most evident in the last, presumably the unhealthiest cluster. High fasting insulin levels and large adipocyte diameter were the predominant clinical characteristic of the heavy co-twins in this cluster (Bonferroni adjusted p<0.05). Conclusions This is the first study in BMI-discordant MZ twin pairs reporting sub-types of obesity based on both SAT gene expression profiles and clinical traits. We conclude that a decrease in mitochondrial BCAA degradation and an increase in inflammation in SAT co-occur and associate with hyperinsulinemia and large adipocyte size in unhealthy obesity.

Project description:The expression level for 15 887 transcripts in lymphoblastoid cell lines from 19 monozygotic twin pairs (10 male, 9 female) were analysed for the effects of genotype and sex. On an average, the effect of twin pairs explained 31% of the variance in normalized gene expression levels, consistent with previous broad sense heritability estimates. The effect of sex on gene expression levels was most noticeable on the X chromosome, which contained 15 of the 20 significantly differentially expressed genes. A high concordance was observed between the sex difference test statistics and surveys of genes escaping X chromosome inactivation. Notably, several autosomal genes showed significant differences in gene expression between the sexes despite much of the cellular environment differences being effectively removed in the cell lines. A publicly available gene expression data set from the CEPH families was used to validate the results. The heritability of gene expression levels as estimated from the two data sets showed a highly significant positive correlation, particularly when both estimates were close to one and thus had the smallest standard error. There was a large concordance between the genes significantly differentially expressed between the sexes in the two data sets. Analysis of the variability of probe binding intensities within a probe set indicated that results are robust to the possible presence of polymorphisms in the target sequences. Keywords: Monozygotic twin pair Expression Profiles Genome-wide gene expression in lymphoblastoid cell lines was determined using microarrays derived from 15 monozygotic (MZ) twin pairs (10 male, 9 female). 10 twin pair are discordant, 4 are concordant for a disease phenotype and their are 5 controls which have no disease phenotype. This data set was analyzed to interrupt replicated effects of sex and genotype, not disease characteristics. Subsets of these samples have been analyzed separately for disease characteristics, (GSE7036 M-bM-^@M-^S 3 MZ twins discordant for bipolar disorder) and (GSE7486 - 5 discordant and 4 concordant MZ twin pairs with idiopathic absence epilepsies and 5 unaffected MZ twin pairs).

Dataset Information

DNA methylome analysis of human peripheral blood samples in cancer discordant monozygotic twin-pairs

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets