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Transcriptome and DNA Methylome Analyses Reveal Underlying Mechanisms for the Racial Disparity in Uterine Fibroids [EPIC Human Methylation Array]

ABSTRACT: Transcriptome and DNA Methylome Analyses Reveal Underlying Mechanisms for the Racial Disparity in Uterine Fibroids [EPIC Human Methylation Array]

PROVIDER: PRJNA854909 | ENA |

REPOSITORIES: ENA

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Transcriptome and DNA Methylome Analyses Reveal Underlying Mechanisms for the Racial Disparity in Uterine Fibroids [EPIC Human Methylation Array]

Project description:Genome wide DNA methylation profiling of normal myometrial and fibroid samples. Uterine fibroids (leiomyomas) affect Black women disproportionately in terms of prevalence, incidence, and severity of symptoms. The causes of this racial disparity are essentially unknown. We hypothesized that myometria of Black women are more susceptible to developing fibroids and examined the transcriptomic and DNA methylation profiles of myometria and fibroids from Black and White women for comparison. Myometrial samples cluster by race in both their transcriptome and DNA methylation profiles, whereas fibroid samples only cluster by race in the latter. More differentially expressed genes (DEGs) were detected in the Black and White myometrial comparison than in the fibroid comparison. Leiomyoma gene set expression analysis showed four different clusters of DEGs, including a cluster with highest expression in Black myometrial samples and elevated in all fibroids. One of the DEGs in this group, VWF, was significantly hypomethylated at two CpG probes near a putative enhancer site in Black myometrial and in all fibroid samples compared with White myometrial samples, suggesting that VWF expression is responsive to DNA hypomethylation, a known stress response. These results suggest that the molecular basis for the disparity in fibroid disease between Black and White women could be found in the myometria before fibroid development and not in the fibroids themselves.

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Project description:Uterine fibroids (leiomyomas) affect Black women disproportionately in terms of prevalence, incidence, and severity of symptoms. The causes of this racial disparity are essentially unknown. We hypothesized that myometria of Black women are more susceptible to developing fibroids and examined the transcriptomic and DNA methylation profiles of myometria and fibroids from Black and White women for comparison. Myometrial samples cluster by race in both their transcriptome and DNA methylation profiles, whereas fibroid samples only cluster by race in the latter. More differentially expressed genes (DEGs) were detected in the Black and White myometrial comparison than in the fibroid comparison. Leiomyoma gene set expression analysis showed four different clusters of DEGs, including a cluster with highest expression in Black myometrial samples and elevated in all fibroids. One of the DEGs in this group, VWF, was significantly hypomethylated at two CpG probes near a putative enhancer site in Black myometrial and in all fibroid samples compared with White myometrial samples, suggesting that VWF expression is responsive to DNA hypomethylation, a known stress response. These results suggest that the molecular basis for the disparity in fibroid disease between Black and White women could be found in the myometria before fibroid development and not in the fibroids themselves.

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Transcriptome and DNA Methylome Analyses Reveal Underlying Mechanisms for the Racial Disparity in Uterine Fibroids [RNA-seq]

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