Variability of genome-wide DNA methylation and mRNA expression profiles in reproductive and endocrine disease related tissues 机翻标题: 暂无翻译,请尝试点击翻译按钮。

来源
Epigenetics: official journal of the DNA Methylation Society
年/卷/期
2017 / 12 / 10
页码
897-908
ISSN号
1559-2294
作者单位
Univ Oxford, Wellcome Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England;Univ Oxford, Wellcome Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England;Univ Oxford, Wellcome Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England;Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Endometriosis CaRe Ctr, Oxford;Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Endometriosis CaRe Ctr, Oxford;Competence Ctr Hlth Technol, Tartu, Estonia;Competence Ctr Hlth Technol, Tartu, Estonia;Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Endometriosis CaRe Ctr, Oxford;Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Endometriosis CaRe Ctr, Oxford;Univ Oxford, Wellcome Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England;Competence Ctr Hlth Technol, Tartu, Estonia;Univ Oxford, Wellcome Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England;Univ Oxford, Wellcome Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England;Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Endometriosis CaRe Ctr, Oxford;Univ Oxford, Wellcome Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England;
作者
Rahmioglu, Nilufer;Drong, Alexander W.;Lockstone, Helen;Tapmeier, Thomas;Hellner, Karin;Saare, Merli;Laisk-Podar, Triin;Dew, Christine;Tough, Emily;Nicholson, George;Peters, Maire;Morris, Andrew P.;Lindgren, Cecilia M.;Becker, Christian M.;Zondervan, Krina T.;
摘要
Genome-wide association studies in the fields of reproductive medicine and endocrinology are yielding robust genetic variants associated with disease. Integrated genomic, transcriptomic, and epigenomic molecular profiling studies are common methodologies used to understand the biologic pathways perturbed by these variants. However, molecular profiling resources do not include the tissue most relevant to many female reproductive traits, the endometrium, while the parameters influencing variability of results from its molecular profiling are unclear. We investigated the sources of DNA methylation and RNA expression profile variability in endometrium (n = 135), endometriotic disease tissue (endometriosis), and subcutaneous abdominal fat samples from 24 women, quantifying between-individual, within-tissue (cellular heterogeneity), and technical variation. DNA samples (n = 96) were analyzed using Illumina HumanMethlylation450 BeadChip arrays; RNA samples (n = 39) were analyzed using H12-expression arrays. Variance-component analyses showed that, for the top 10-50% variable DNA methylation/RNA expression sites, between-individual variation far exceeded within-tissue and technical variation. Menstrual-phase accounted for most variability in methylation/ expression patterns in endometrium (P-m = 7.8 x 10(-3), Pe = 8.4 x 10(-5)) but not in fat and endometriotic tissue; age was significantly associated with DNA methylation profile of endometrium (P-m = 9 x 10(-5)) and endometriotic disease tissue (P-m = 2.4 x 10(-5)); and smoking was significantly associated with DNA methylation in adipose tissue (P-m = 1.8 x 10(-3)). Hierarchical cluster analysis showed significantly different methylation signatures between endometrium and endometriotic tissue enriched for WNT signaling, angiogenesis, cadherin signaling, and gonadotropin-releasing-hormone-receptor pathways. Differential DNA methylation/ expression analyses suggested detection of a limited number of sites with large fold changes (FC > 4), but power calculations accounting for different sources of variability showed that for robust detection > 500 tissue samples are required. These results enable appropriate study design for large-scale expression and methylation tissue-based profiling relevant to many reproductive and endocrine traits.
机翻摘要
暂无翻译结果,您可以尝试点击头部的翻译按钮。
关键词/主题词
DNA methylation;endometrium;endocrine;endometriosis;gene expression;reproductive;
若您需要申请原文,请登录。

最新评论

暂无评论。

登录后可以发表评论

意见反馈
返回顶部