DNA methylation contributes to natural human variation
Holger Heyn,Sebastian Moran,Irene Hernando-Herraez,Sergi Sayols,Antonio Gomez,Juan Sandoval,Dave Monk,Kenichiro Hata,Tomas Marques-Bonet,Tomas Marques-Bonet,Liewei Wang,Manel Esteller,Manel Esteller +12 more
Reads0
Chats0
TLDR
In this article, the contribution of DNA methylation patterns to variability in human variation was investigated, and it was found that one third of the differences were not associated with any genetic variation, suggesting that variation in population-specific sites takes place at the genetic and epigenetic levels.Abstract:
DNA methylation patterns are important for establishing cell, tissue, and organism phenotypes, but little is known about their contribution to natural human variation. To determine their contribution to variability, we have generated genome-scale DNA methylation profiles of three human populations (Caucasian-American, African-American, and Han Chinese-American) and examined the differentially methylated CpG sites. The distinctly methylated genes identified suggest an influence of DNA methylation on phenotype differences, such as susceptibility to certain diseases and pathogens, and response to drugs and environmental agents. DNA methylation differences can be partially traced back to genetic variation, suggesting that differentially methylated CpG sites serve as evolutionarily established mediators between the genetic code and phenotypic variability. Notably, one-third of the DNA methylation differences were not associated with any genetic variation, suggesting that variation in population-specific sites takes place at the genetic and epigenetic levels, highlighting the contribution of epigenetic modification to natural human variation.read more
Citations
More filters
Journal ArticleDOI
The role of regulatory variation in complex traits and disease
Frank W. Albert,Leonid Kruglyak +1 more
TL;DR: Recent insights into the molecular nature of regulatory variants are reviewed and examples of complete chains of causality that link individual polymorphisms to changes in gene expression, which in turn result in physiological changes and, ultimately, disease risk are presented.
Journal ArticleDOI
Validation of a DNA methylation microarray for 850,000 CpG sites of the human genome enriched in enhancer sequences
TL;DR: The 850K array demonstrates high reproducibility at the 450K CpG sites, is consistent among technical replicates, is reliable in the matched study of fresh frozen versus formalin-fixed paraffin-embeded samples and is also useful for 5-hydroxymethylcytosine.
Journal ArticleDOI
Preprocessing, normalization and integration of the Illumina HumanMethylationEPIC array with minfi.
TL;DR: Modifications to the minfi package required to support the HumanMethylationEPIC (‘EPIC’) array from Illumina are described and the single‐sample Noob (ssNoob) method is introduced, a normalization procedure suitable for incremental preprocessing of individual methylation arrays and concluded that this method should be used when integrating data from multiple generations of Infinium methylation array.
Journal ArticleDOI
An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease
Steve Horvath,Michael Gurven,Morgan E. Levine,Benjamin C. Trumble,Hillard Kaplan,Hooman Allayee,Beate Ritz,Brian H. Chen,Ake T. Lu,Tammy M. Rickabaugh,Beth D. Jamieson,Dianjianyi Sun,Shengxu Li,Wei Chen,Lluis Quintana-Murci,Maud Fagny,Michael S. Kobor,Philip S. Tsao,Philip S. Tsao,Alexander P. Reiner,Kerstin L. Edlefsen,Devin Absher,Themistocles L. Assimes +22 more
TL;DR: Epigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes.
Journal ArticleDOI
Systematic identification of genetic influences on methylation across the human life course
Tom R. Gaunt,Hashem A. Shihab,Gibran Hemani,Josine L. Min,G. Woodward,Oliver Lyttleton,Jie Zheng,Aparna Duggirala,Wendy L. McArdle,Karen M Ho,Susan M. Ring,David M. Evans,David M. Evans,George Davey Smith,Caroline L Relton,Caroline L Relton +15 more
TL;DR: It is suggested that methylation may have a causal role consistent with an infinitesimal model in which many methylation sites each have a small influence, amounting to a large overall contribution.
References
More filters
Journal Article
R: A language and environment for statistical computing.
TL;DR: Copyright (©) 1999–2012 R Foundation for Statistical Computing; permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and permission notice are preserved on all copies.
Journal ArticleDOI
Fast and accurate short read alignment with Burrows–Wheeler transform
Heng Li,Richard Durbin +1 more
TL;DR: Burrows-Wheeler Alignment tool (BWA) is implemented, a new read alignment package that is based on backward search with Burrows–Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps.
Journal ArticleDOI
PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
Shaun Purcell,Shaun Purcell,Benjamin M. Neale,Benjamin M. Neale,Kathe Todd-Brown,Lori Thomas,Manuel A. R. Ferreira,David Bender,David Bender,Julian Maller,Julian Maller,Pamela Sklar,Pamela Sklar,Paul I.W. de Bakker,Paul I.W. de Bakker,Mark J. Daly,Mark J. Daly,Pak C. Sham +17 more
TL;DR: This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.
Classification and Regression by randomForest
Andy Liaw,Matthew C. Wiener +1 more
TL;DR: random forests are proposed, which add an additional layer of randomness to bagging and are robust against overfitting, and the randomForest package provides an R interface to the Fortran programs by Breiman and Cutler.
Journal ArticleDOI
An integrated encyclopedia of DNA elements in the human genome
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
Related Papers (5)
Epigenetic differences arise during the lifetime of monozygotic twins
Mario F. Fraga,Esteban Ballestar,Maria F. Paz,Santiago Ropero,Fernando Setien,Maria Luisa Ballestar,Damia Heine-Suñer,Juan C. Cigudosa,Miguel Urioste,Javier Benitez,Manuel Boix-Chornet,Abel Sánchez-Aguilera,Charlotte Ling,Emma Carlsson,Pernille Poulsen,Allan Vaag,Zarko Stephan,Tim D. Spector,Yue Zhong Wu,Christoph Plass,Manel Esteller +20 more