Personalized Epigenomic Signatures That Are Stable Over Time and Covary with Body Mass Index
Andrew P. Feinberg,Andrew P. Feinberg,Rafael A. Irizarry,Delphine Fradin,Delphine Fradin,Martin J. Aryee,Peter Murakami,Peter Murakami,Thor Aspelund,Gudny Eiriksdottir,Tamara B. Harris,Lenore J. Launer,Vilmundur Gudnason,M. Daniele Fallin +13 more
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TLDR
A genome-scale, gene-specific analysis of DNA methylation in the same individuals over a decade apart identifies a personalized epigenomic signature that may correlate with a common genetic trait.Abstract:
The epigenome consists of non–sequence-based modifications, such as DNA methylation, that are heritable during cell division and that may affect normal phenotypes and predisposition to disease. Here, we have performed an unbiased genome-scale analysis of ~4 million CpG sites in 74 individuals with comprehensive array-based relative methylation (CHARM) analysis. We found 227 regions that showed extreme interindividual variability [variably methylated regions (VMRs)] across the genome, which are enriched for developmental genes based on Gene Ontology analysis. Furthermore, half of these VMRs were stable within individuals over an average of 11 years, and these VMRs defined a personalized epigenomic signature. Four of these VMRs showed covariation with body mass index consistently at two study visits and were located in or near genes previously implicated in regulating body weight or diabetes. This work suggests an epigenetic strategy for identifying patients at risk of common disease.read more
Citations
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Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates
Gregory Hannum,Justin Guinney,Ling Zhao,Ling Zhao,Li Zhang,Guy Hughes,Srinivas R. Sadda,Brandy Klotzle,Marina Bibikova,Jian-Bing Fan,Yuan Gao,Rob Deconde,Menzies Chen,Indika Rajapakse,Stephen H. Friend,Trey Ideker,Kang Zhang,Kang Zhang +17 more
TL;DR: A quantitative model of aging is built using measurements at more than 450,000 CpG markers from the whole blood of 656 human individuals, aged 19 to 101, to measure the rate at which an individual's methylome ages, which is impacted by gender and genetic variants.
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Epigenome-wide association studies for common human diseases
TL;DR: This work discusses EWAS design, cohort and sample selections, statistical significance and power, confounding factors and follow-up studies, and how integration of EWASs with GWASs can help to dissect complex GWAS haplotypes for functional analysis.
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Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis
Yun Liu,Martin J. Aryee,Leonid Padyukov,M. Daniele Fallin,M. Daniele Fallin,Espen Hesselberg,Arni Runarsson,Lovisa E. Reinius,Nathalie Acevedo,Margaret A. Taub,Margaret A. Taub,Marcus Ronninger,Klementy Shchetynsky,Annika Scheynius,Juha Kere,Lars Alfredsson,Lars Klareskog,Tomas J. Ekström,Andrew P. Feinberg,Andrew P. Feinberg +19 more
TL;DR: DNA methylation is a potential mediator of genetic risk for rheumatoid arthritis and is corrected for cellular heterogeneity by estimating and adjusting for cell-type proportions in blood-derived DNA samples and used mediation analysis to filter out associations likely to be a consequence of disease.
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Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci.
Philip L. De Jager,Gyan Srivastava,Katie Lunnon,Jeremy D. Burgess,Leonard C. Schalkwyk,Lei Yu,Matthew L. Eaton,Brendan T. Keenan,Jason Ernst,Cristin McCabe,Anna Tang,Towfique Raj,Joseph M. Replogle,Wendy Brodeur,Stacey Gabriel,High Seng Chai,Curtis S. Younkin,Steven G. Younkin,Fanggeng Zou,Moshe Szyf,Charles B. Epstein,Julie A. Schneider,Bradley E. Bernstein,Alexander Meissner,Nilufer Ertekin-Taner,Lori B. Chibnik,Manolis Kellis,Jonathan Mill,David A. Bennett +28 more
TL;DR: The analyses suggest that DNA methylation changes may have a role in the onset of AD given that they were observed in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network.
Journal ArticleDOI
DNA methylation and body-mass index: a genome-wide analysis
Katherine J. Dick,Katherine J. Dick,Christopher P. Nelson,Christopher P. Nelson,Loukia Tsaprouni,Johanna K. Sandling,Johanna K. Sandling,Dylan Aïssi,Dylan Aïssi,Dylan Aïssi,Simone Wahl,Eshwar Meduri,Pierre-Emmanuel Morange,Harald Grallert,Melanie Waldenberger,Annette Peters,Jeanette Erdmann,Christian Hengstenberg,François Cambien,François Cambien,François Cambien,Alison H. Goodall,Alison H. Goodall,Willem H. Ouwehand,Willem H. Ouwehand,Willem H. Ouwehand,Heribert Schunkert,John R. Thompson,Tim D. Spector,Christian Gieger,David-Alexandre Trégouët,David-Alexandre Trégouët,David-Alexandre Trégouët,Panos Deloukas,Panos Deloukas,Panos Deloukas,Nilesh J. Samani,Nilesh J. Samani +37 more
TL;DR: Increased BMI in adults of European origin is associated with increased methylation at the HIF3A locus in blood cells and in adipose tissue, and perturbation of hypoxia inducible transcription factor pathways could have an important role in the response to increased weight in people.
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