Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
33582897
TITLE
The Augmented Classical Twin Design: Incorporating Genome-Wide Identity by Descent Sharing Into Twin Studies in Order to Model Violations of the Equal Environments Assumption.
ABSTRACT
The Classical Twin Method (CTM) compares the similarity of monozygotic (MZ) twins with that of dizygotic (DZ) twins to make inferences about the relative importance of genes and environment in the etiology of individual differences. The design has been applied to thousands of traits across the biomedical, behavioral and social sciences and is arguably the most widely used natural experiment known to science. The fundamental assumption of the CTM is that trait relevant environmental covariation within MZ pairs is the same as that found within DZ pairs, so that zygosity differences in within-pair variance must be due to genetic factors uncontaminated by the environment. This equal environments assumption (EEA) has been, and still is hotly contested, and has been mentioned as a possible contributing factor to the missing heritability conundrum. In this manuscript, we introduce a new model for testing the EEA, which we call the Augmented Classical Twin Design which uses identity by descent (IBD) sharing between DZ twin pairs to estimate separate environmental variance components for MZ and DZ twin pairs, and provides a test of whether these are equal. We show through simulation that given large samples of DZ twin pairs, the model provides unbiased estimates of variance components and valid tests of the EEA under strong assumptions (e.g. no epistatic variance, IBD sharing in DZ twins estimated accurately etc.) which may not hold in reality. Sample sizes in excess of 50,000 DZ twin pairs with genome-wide genetic data are likely to be required in order to detect substantial violations of the EEA with moderate power. Consequently, we recommend that the Augmented Classical Twin Design only be applied to datasets with very large numbers of DZ twin pairs (> 50,000 DZ twin pairs), and given the strong assumptions relating to the absence of epistatic variance, appropriate caution be exercised regarding interpretation of the results.
DATE PUBLISHED
2021 Feb 13
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2020/08/25
accepted 2021/01/21
entrez 2021/02/14 20:38
pubmed 2021/02/15 06:00
medline 2021/02/15 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Hwang LD Hwang Liang-Dar LD QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Mitchell BL Mitchell Brittany L BL School of Biomedical Science, Institute of Health and Biomedical Innovation, Faculty of Health, Queensland University of Technology (QUT), Brisbane, Australia.
Medland SE Medland Sarah E SE QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Martin NG Martin Nicholas G NG School of Biomedical Science, Institute of Health and Biomedical Innovation, Faculty of Health, Queensland University of Technology (QUT), Brisbane, Australia.
Neale MC Neale Michael C MC Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Evans DM Evans David M DM Translational Research Institute, Woolloongabba, QLD, 4102, Australia. d.evans1@uq.edu.au.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Behavior genetics
ISOABBREVIATION: Behav Genet
YEAR: 2021
MONTH: Feb
DAY: 13
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1573-3297
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Behav Genet
COUNTRY: United States
ISSNLINKING: 0001-8244
NLMUNIQUEID: 0251711
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
APP1137714 National Health and Medical Research Council
APP 1103623 National Health and Medical Research Council
GENERAL NOTE
KEYWORDS
KEYWORD
Equal environment assumption
Heritability
Identity by descent
Twin studies
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's