X Inactivation as a Source of Behavioural Differences in Monozygotic Female Twins

Loat, Caroline S.; Asbury, Kathryn; Galsworthy, Michael J.; Plomin, Robert; Craig, Ian W.

doi:10.1375/13690520460741444

Cited by 38 publications

(20 citation statements)

References 33 publications

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“…Third, for developmental disorders, twins offer the perfect age-matched within-family comparison to protect against spurious associations due to population stratification. In addition, MZ twins offer a unique opportunity to study epigenetic differences such as Xinactivation (Loat et al, 2004).…”

Section: Molecular Genetic Findingsmentioning

confidence: 99%

Twins' Early Development Study (TEDS): A Multivariate, Longitudinal Genetic Investigation of Language, Cognition and Behavior Problems from Childhood Through Adolescence

2007

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The Twins' Early Development Study (TEDS) is a large-scale longitudinal study of twins from early childhood through adolescence. Since its conception, TEDS has had as its focus the study of problematic development within the context of normal variation, mainly in the development of language, cognitive and academic abilities and behavior problems from multivariate quantitative and molecular genetic perspectives. TEDS twins have been assessed at 2, 3, 4, 7, 9, 10 and (currently) 12 years of age, and DNA collected from more than 12,000 children. Identified from birth records of twins born in the United Kingdom between 1994 and 1996, more than 15,000 pairs of twins originally enrolled in TEDS, and well over 13,000 pairs — representative of the UK population — remain involved in the study to date. Similar to many other twin and adoption studies, TEDS data indicate that both genetic and environmental influences are important in nearly all areas of behavioral development. Multivariate genetic analyses allow researchers to go beyond this basic nature–nurture question, and TEDS results suggest that, especially in the area of learning abilities and disabilities, genes are generalists and environments are specialists. That is, genes largely contribute to similarity in performance within and between learning abilities and disabilities and across age, whereas the environment contributes to differences in performance. Quantitative genetic findings such as these chart the course for molecular genetic research. The TEDS dataset is proving valuable in genome-wide association research that tries to identify some of the many genes responsible for the ubiquitous heritability of behavior.

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Section: Molecular Genetic Findingsmentioning

confidence: 99%

Twins' Early Development Study (TEDS): A Multivariate, Longitudinal Genetic Investigation of Language, Cognition and Behavior Problems from Childhood Through Adolescence

2007

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“…Loat and colleagues. 80 have argued that given the random nature of X inactivation, female MZ twin pairs do not necessarily inactivate the same X chromosome and will thus show higher levels of discordance than male MZ twin pairs. To our knowledge, no study has yet tested this theory on individuals with MDD, but analyses on MZ twins assessed at ages 2, 3 and 4 suggests that this pattern is observed for a number of behavioural traits closely related to depression.…”

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confidence: 99%

“…To our knowledge, no study has yet tested this theory on individuals with MDD, but analyses on MZ twins assessed at ages 2, 3 and 4 suggests that this pattern is observed for a number of behavioural traits closely related to depression. 80 Another epigenetic phenomenon that may confound X-linked gene studies in MDD is the existence of genes escaping X inactivation. Not all genes on the X chromosome are inactivated, with as many as 15% showing evidence of expression from both X chromosomes.…”

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confidence: 99%

Molecular studies of major depressive disorder: the epigenetic perspective

2007

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Major depressive disorder (MDD) is a common and highly heterogeneous psychiatric disorder encompassing a spectrum of symptoms involving deficits to a range of cognitive, psychomotor and emotional processes. As is the norm for aetiological studies into the majority of psychiatric phenotypes, particular focus has fallen on the interplay between genetic and environmental factors. There are, however, several epidemiological, clinical and molecular peculiarities associated with MDD that are hard to explain using traditional geneand environment-based approaches. Our goal in this study is to demonstrate the benefits of looking beyond conventional 'DNA þ environment' and 'DNA Â environment' aetiological paradigms. Epigenetic factors -inherited and acquired modifications of DNA and histones that regulate various genomic functions occurring without a change in nuclear DNA sequence -offer new insights about many of the non-Mendelian features of major depression, and provide a direct mechanistic route via which the environment can interact with the genome. The study of epigenetics, especially in complex diseases, is a relatively new field of research, and optimal laboratory techniques and analysis methods are still being developed. Incorporating epigenetic research into aetiological studies of MDD thus presents a number of methodological and interpretive challenges that need to be addressed. Despite these difficulties, the study of DNA methylation and histone modifications has the potential to transform our understanding about the molecular aetiology of complex diseases.

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“…If polymorphic X-linked loci are involved, FMZ pairs should be more discordant than MMZ due to skewed X-inactivation [Rosa et al, 2008]. This was observed by Loat et al [2004] in a study that tested a large sample of same-sex twin pairs on several social, behavioral, and cognitive measures: concordance rates were higher in almost all categories in MMZ twins than in FMZ twins.…”

Section: Differential Epigenetic Profiles In Twins: Skewed X-inactivamentioning

confidence: 92%

“…Traits showing higher concordance rates in males included pro-social behavior, peer problems, and verbal ability, all of which are influenced by genes on the X chromosome [Loat et al, 2004]. In schizophrenia, some evidence points to the possibility that the disease may be X-linked and thus modulated by skewed X-inactivation: An excess of X-chromosome aneuploidies (XXX and XXY) among patients has been found in a subgroup of familial cases [DeLisi et al, 1994;Rosa et al, 2008], and MZ twin concordance for psychosis is slightly higher in males than females [Rosa et al, 2008].…”

Section: Differential Epigenetic Profiles In Twins: Skewed X-inactivamentioning

confidence: 99%

Not really identical: Epigenetic differences in monozygotic twins and implications for twin studies in psychiatry

Haque

Gottesman

Wong

2009

American J of Med Genetics Pt C

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Classical twin studies in the field of psychiatry generally fall into one of two categories: (1) those designed to identify environmental risk factors causing discordance in monozygotic (MZ) twins and (2) those geared towards identifying genetic risk factors. However, neither environment nor differences in DNA sequence can fully account for phenotypic discordance among MZ twins. The field of epigenetics -DNA modifications that can affect gene expression -offers new models to understand discordance in MZ twins. In the past, MZ twins were regarded as genetically-identical controls for differing environmental conditions. In contrast, the evolving current concept is that epigenetic differences between MZ twins may modulate differences in diverse phenotype, from disease to personality. In this article, we review some twin studies, and discuss the dynamic interactions between stochastic, environmental, and epigenetic variables that influence neurobiological phenotypes. ß

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X Inactivation as a Source of Behavioural Differences in Monozygotic Female Twins

Cited by 38 publications

References 33 publications

Twins' Early Development Study (TEDS): A Multivariate, Longitudinal Genetic Investigation of Language, Cognition and Behavior Problems from Childhood Through Adolescence

Twins' Early Development Study (TEDS): A Multivariate, Longitudinal Genetic Investigation of Language, Cognition and Behavior Problems from Childhood Through Adolescence

Molecular studies of major depressive disorder: the epigenetic perspective

Not really identical: Epigenetic differences in monozygotic twins and implications for twin studies in psychiatry

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