A quantitative genetic and epigenetic model of complex traits

BackgroundDespite our increasing recognition of the mechanisms that specify and propagate epigenetic states of gene expression, the pattern of how epigenetic modifications contribute to the overall genetic variation of a phenotypic trait remains largely elusive.ResultsWe construct a quantitative model to explore the effect of epigenetic modifications that occur at specific rates on the genome. This model, derived from, but beyond, the traditional quantitative genetic theory that is founded on Mendel’s laws, allows questions concerning the prevalence and importance of epigenetic variation to be incorporated and addressed.ConclusionsIt provides a new avenue for bringing chromatin inheritance into the realm of complex traits, facilitating our understanding of the means by which phenotypic variation is generated.

[1]  R. Jansen,et al.  Epigenome dynamics: a quantitative genetics perspective , 2008, Nature Reviews Genetics.

[2]  Guifang Fu,et al.  The Bayesian lasso for genome-wide association studies , 2011, Bioinform..

[3]  Rongling Wu,et al.  A computational framework for the inheritance pattern of genomic imprinting for complex traits , 2012, Briefings Bioinform..

[4]  R. Wu,et al.  A General Model for Multilocus Epistatic Interactions in Case-Control Studies , 2010, PloS one.

[5]  E. Richards Inherited epigenetic variation — revisiting soft inheritance , 2006, Nature Reviews Genetics.

[6]  Patrick S. Schnable,et al.  Heritable Epigenetic Variation among Maize Inbreds , 2011, PLoS genetics.

[7]  Steven Henikoff,et al.  Quantitative epigenetics , 2003, Nature Genetics.

[8]  E. Richards Natural epigenetic variation in plant species: a view from the field. , 2011, Current opinion in plant biology.

[9]  B. Maher Personal genomes: The case of the missing heritability , 2008, Nature.

[10]  R. Tibshirani,et al.  Regression shrinkage and selection via the lasso: a retrospective , 2011 .

[11]  E. Richards,et al.  Quantitative epigenetics: DNA sequence variation need not apply. , 2009, Genes & development.

[12]  Jason H. Moore,et al.  Missing heritability and strategies for finding the underlying causes of complex disease , 2010, Nature Reviews Genetics.

[13]  Wim E Crusio AN INTRODUCTION TO QUANTITATIVE GENETICS , 1998 .

[14]  A. Feinberg,et al.  Stochastic epigenetic variation as a driving force of development, evolutionary adaptation, and disease , 2010, Proceedings of the National Academy of Sciences.

[15]  Massimo Pigliucci,et al.  What Role Does Heritable Epigenetic Variation Play in Phenotypic Evolution? , 2010 .

[16]  A. G. Abbott,et al.  Genetic mapping of quantitative trait loci. , 2008 .

[17]  BMC Bioinformatics , 2005 .

[18]  E. Whitelaw,et al.  Transgenerational epigenetic inheritance in health and disease. , 2008, Current opinion in genetics & development.

[19]  Montgomery Slatkin,et al.  Epigenetic Inheritance and the Missing Heritability Problem , 2009, Genetics.

[20]  Frank Johannes,et al.  Assessing the Impact of Transgenerational Epigenetic Variation on Complex Traits , 2009, PLoS genetics.

[21]  Detlef Weigel,et al.  On epigenetics and epistasis: hybrids and their non‐additive interactions , 2012, The EMBO journal.

[22]  J. Arand,et al.  Epigenetic Reprogramming in Mammalian Development , 2012 .

[23]  A. Parekh The Wellcome Prize Lecture , 2003 .

[24]  Arturas Petronis,et al.  Epigenetics as a unifying principle in the aetiology of complex traits and diseases , 2010, Nature.

[25]  M. Colomé-Tatché,et al.  Quantitative Epigenetics Through Epigenomic Perturbation of Isogenic Lines , 2011, Genetics.

[26]  Rongling Wu,et al.  A Model for Transgenerational Imprinting Variation in Complex Traits , 2010, PloS one.

[27]  R. Tibshirani Regression Shrinkage and Selection via the Lasso , 1996 .

[28]  Jeffrey T Leek,et al.  Significance analysis and statistical dissection of variably methylated regions. , 2012, Biostatistics.

[29]  Ritsert C. Jansen,et al.  Genome-Wide Epigenetic Perturbation Jump-Starts Patterns of Heritable Variation Found in Nature , 2011, Genetics.

[30]  Judy H. Cho,et al.  Finding the missing heritability of complex diseases , 2009, Nature.

[31]  W. Reik The Wellcome Prize Lecture. Genetic imprinting: the battle of the sexes rages on , 1996, Experimental physiology.

[32]  Eva Jablonka,et al.  Epigenetic Contribution to Covariance Between Relatives , 2010, Genetics.

[33]  D. Falconer,et al.  Introduction to Quantitative Genetics. , 1961 .

[34]  A. Feinberg Phenotypic plasticity and the epigenetics of human disease , 2007, Nature.

[35]  N. Youngson,et al.  Transgenerational epigenetic effects. , 2008, Annual review of genomics and human genetics.

[36]  D. Andrews Testing When a Parameter Is on the Boundary of the Maintained Hypothesis , 2001 .

[37]  A. Feinberg,et al.  The history of cancer epigenetics , 2004, Nature Reviews Cancer.

[38]  Rafael A. Irizarry,et al.  Personalized Epigenomic Signatures That Are Stable Over Time and Covary with Body Mass Index , 2010, Science Translational Medicine.

[39]  W. Ewens Genetics and analysis of quantitative traits , 1999 .

[40]  Rongling Wu,et al.  A Statistical Design for Testing Transgenerational Genomic Imprinting in Natural Human Populations , 2011, PloS one.

[41]  W. Reik,et al.  Epigenetic Reprogramming in Mammalian Development , 2001, Science.

[42]  K. Liang,et al.  Asymptotic Properties of Maximum Likelihood Estimators and Likelihood Ratio Tests under Nonstandard Conditions , 1987 .

[43]  Martin J. Aryee,et al.  Personalized Epigenomic Signatures That Are Stable Over Time and Covary with Body Mass Index , 2010, Science Translational Medicine.

[44]  J. Cavanaugh Biostatistics , 2005, Definitions.

[45]  Rongling Wu,et al.  Asymptotic distribution for epistatic tests in case-control studies. , 2011, Genomics.

[46]  Rongling Wu,et al.  Modeling Haplotype-Haplotype Interactions in Case-Control Genetic Association Studies , 2012, Front. Gene..

[47]  Marcus W. Feldman,et al.  Environment-Sensitive Epigenetics and the Heritability of Complex Diseases , 2011, Genetics.