Combining twin-family designs with measured genetic variants to study the causes of epigenetic variation

Camelia C. Minică, Michael C. Neale, Dorret I. Boomsma, Jenny van Dongen

Research output: Chapter in Book / Report / Conference proceedingChapterAcademicpeer-review

Abstract

Classical twin and family designs can be applied to examine the contribution of genetic and environmental influences to variation in epigenetic marks. Such models can be extended to allow for more in-depth questions, such as: How much of the variation in DNA methylation is explained by methylation Quantitative Trait Loci (QTLs)? Does the contribution of genetic or environmental influences differ between males and females or between younger and older individuals? Does methylation level at CpG site X have a causal effect on trait Y and vice versa, or is the association driven by genetic pleiotropy? In this chapter, we discuss twin designs that allow to address these questions. First, we describe models that incorporate genetic relationships based on genome-wide SNP data and the application of such models to DNA methylation data from adult twins and family members. Second, we discuss the value of an integration of Mendelian Randomization (MR) with the classical twin design.

Original languageEnglish
Title of host publicationTwin and Family Studies of Epigenetics
EditorsS. Li, J. Hopper
PublisherElsevier
Chapter13
Pages239-259
Number of pages21
Volume27
ISBN (Electronic)9780128209523
ISBN (Print)9780128209516
DOIs
Publication statusPublished - 2021

Publication series

NameTranslational Epigenetics
PublisherElsevier
Volume27

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Inc. All rights reserved.

Keywords

  • Causality
  • Direction of causation (DOC)
  • DNA methylation
  • Epigenetics
  • Genetic relatedness matrix (GRM)
  • Heritability
  • Mendelian Randomization (MR)
  • Mendelian Randomization-direction of causation model (MR-DoC)
  • Single nucleotide polymorphism (SNP) heritability
  • Twins

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