Common disorders are quantitative traits Plomin, Robert; Haworth, Claire M. A; Davis, Oliver S. P
Nature reviews. Genetics,
12/2009, Letnik:
10, Številka:
12
Journal Article
Recenzirano
After drifting apart for 100 years, the two worlds of genetics - quantitative genetics and molecular genetics - are finally coming together in genome-wide association (GWA) research, which shows that ...the heritability of complex traits and common disorders is due to multiple genes of small effect size. We highlight a polygenic framework, supported by recent GWA research, in which qualitative disorders can be interpreted simply as being the extremes of quantitative dimensions. Research that focuses on quantitative traits - including the low and high ends of normal distributions - could have far-reaching implications for the diagnosis, treatment and prevention of the problematic extremes of these traits.
The Twins Early Development Study (TEDS) is a large longitudinal sample of twins born in England and Wales between 1994 and 1996. The focus of TEDS has been on cognitive and behavioral development, ...including difficulties in the context of normal development. TEDS began when multiple births were identified from birth records and the families were invited to take part in the study; 16,810 pairs of twins were originally enrolled in TEDS. More than 10,000 of these twin pairs remain enrolled in the study to date. DNA has been collected for more than 7,000 pairs, and genome-wide genotyping data for two million DNA markers are available for 3,500 individuals. The TEDS families have taken part in studies when the twins were aged 2, 3, 4, 7, 8, 9, 10, 12, 14, and 16 years of age. Data collection is currently underway to assess the adult destinations of the twins as they move from school to university and the workplace. Between January 2012 and December 2014, all of the TEDS twins will turn 18, and the study will transition to an adult sample. TEDS represents an outstanding resource for investigating the developmental effects of genes and environments on complex quantitative traits from childhood to young adulthood and beyond.
The environment can moderate the effect of genes - a phenomenon called gene-environment (GxE) interaction. Several studies have found that socioeconomic status (SES) modifies the heritability of ...children's intelligence. Among low-SES families, genetic factors have been reported to explain less of the variance in intelligence; the reverse is found for high-SES families. The evidence however is inconsistent. Other studies have reported an effect in the opposite direction (higher heritability in lower SES), or no moderation of the genetic effect on intelligence.
Using 8716 twin pairs from the Twins Early Development Study (TEDS), we attempted to replicate the reported moderating effect of SES on children's intelligence at ages 2, 3, 4, 7, 9, 10, 12 and 14: i.e., lower heritability in lower-SES families. We used a twin model that allowed for a main effect of SES on intelligence, as well as a moderating effect of SES on the genetic and environmental components of intelligence.
We found greater variance in intelligence in low-SES families, but minimal evidence of GxE interaction across the eight ages. A power calculation indicated that a sample size of about 5000 twin pairs is required to detect moderation of the genetic component of intelligence as small as 0.25, with about 80% power - a difference of 11% to 53% in heritability, in low- (-2 standard deviations, SD) and high-SES (+2 SD) families. With samples at each age of about this size, the present study found no moderation of the genetic effect on intelligence. However, we found the greater variance in low-SES families is due to moderation of the environmental effect - an environment-environment interaction.
In a UK-representative sample, the genetic effect on intelligence is similar in low- and high-SES families. Children's shared experiences appear to explain the greater variation in intelligence in lower SES.
Peer victimisation is a common occurrence and has well-established links with a range of psychiatric problems in adulthood. Significantly less is known however, about how victimisation influences ...positive aspects of mental health such as wellbeing. The purpose of this study was therefore to assess for the first time, whether peer victimisation in adolescence is associated with adult wellbeing. We aimed to understand whether individuals who avoid a diagnosis of depression after victimisation, maintain good wellbeing in later life, and therefore display resilience.
Longitudinal data was taken from the Avon Longitudinal Study of Parents and Children, a prospective cohort study based in the UK. Peer victimisation was assessed at 13 years using a modified version of the bullying and friendship interview schedule, and wellbeing at age 23 using the Warwick-Edinburgh Mental Well-Being Scale. The presence or absence of depression was diagnosed using the Clinical Interview Schedule-Revised at 18 years. A series of logistic and linear regression analyses were used to explore relationships between peer victimisation, depression, and wellbeing, adjusting for potentially confounding individual and family factors.
Just over 15% of victims of frequent bullying had a diagnosis of depression at age 18. Victimisation also had a significant impact on wellbeing, with a one-point increase in frequent victimisation associated with a 2.71-point (SE = 0.46, p < 0.001) decrease in wellbeing scores aged 23. This finding remained after adjustment for the mediating and moderating effects of depression, suggesting that the burden of victimisation extends beyond depression to impact wellbeing. Results therefore show that individuals who remain partially resilient by avoiding a diagnosis of depression after victimisation have significantly poorer wellbeing than their non-victimised counterparts.
Overall, our study demonstrates for the first time that victimisation during adolescence is a significant risk factor for not only the onset of depression, but also poor wellbeing in adulthood. Such findings highlight the importance of investigating both dimensions of mental health to understand the true burden of victimisation and subsequent resilience. In addition to the need for interventions that reduce the likelihood of depression following adolescent victimisation, efforts should also be made to promote good wellbeing.
Online media use has become an increasingly important behavioral domain over the past decade. However, studies into the etiology of individual differences in media use have focused primarily on ...pathological use. Here, for the first time, we test the genetic influences on online media use in a UK representative sample of 16 year old twins, who were assessed on time spent on educational (N = 2,585 twin pairs) and entertainment websites (N = 2,614 twin pairs), time spent gaming online (N = 2,635 twin pairs), and Facebook use (N = 4,333 twin pairs). Heritability was substantial for all forms of online media use, ranging from 34% for educational sites to 37% for entertainment sites and 39% for gaming. Furthermore, genetics accounted for 24% of the variance in Facebook use. Our results support an active model of the environment, where young people choose their online engagements in line with their genetic propensities.
Interventions rarely have a universal effect on all individuals. Reasons ranging from participant characteristics, context and fidelity of intervention completion could cause some people to respond ...more positively than others. Understanding these individual differences in intervention response may provide clues to the mechanisms behind the intervention, as well as inform future designs to make interventions maximally beneficial for all. Here we focus on an intervention designed to improve adolescent wellbeing, and explore potential moderators using a representative and well-powered sample. 16-year old participants (N = 932) in the Twins Wellbeing Intervention Study logged online once a week to complete control and wellbeing-enhancing activities consecutively. Throughout the study participants also provided information about a range of potential moderators of intervention response including demographics, seasonality, personality, baseline characteristics, activity fit, and effort. As expected, some individuals gained more from the intervention than others; we used multi-level modelling to test for moderation effects that could explain these individual differences. Of the 15 moderators tested, none significantly explained individual differences in intervention response in the intervention and follow-up phases. Self-reported effort and baseline positive affect had a notable effect in moderating response in the control phase, during which there was no overall improvement in wellbeing and mental health. Our results did not replicate the moderation effects that have been suggested by previous literature and future work needs to reconcile these differences. They also show that factors that have previously been shown to influence baseline wellbeing do not also influence an individual's ability to benefit from a wellbeing intervention. Although future research should continue to explore potential moderators of intervention efficacy, our results suggest that the beneficial effect of positive activities in adolescents were universal across such factors as sex and socioeconomic status, bolstering claims of the scalability of positive activities to increase adolescent wellbeing.
Spatial ability predicts performance in mathematics and eventual expertise in science, technology and engineering. Spatial skills have also been shown to rely on neuronal networks partially shared ...with mathematics. Understanding the nature of this association can inform educational practices and intervention for mathematical underperformance. Using data on two aspects of spatial ability and three domains of mathematical ability from 4174 pairs of 12‐year‐old twins, we examined the relative genetic and environmental contributions to variation in spatial ability and to its relationship with different aspects of mathematics. Environmental effects explained most of the variation in spatial ability (~70%) and in mathematical ability (~60%) at this age, and the effects were the same for boys and girls. Genetic factors explained about 60% of the observed relationship between spatial ability and mathematics, with a substantial portion of the relationship explained by common environmental influences (26% and 14% by shared and non‐shared environments respectively). These findings call for further research aimed at identifying specific environmental mediators of the spatial–mathematics relationship.
Research highlights
About a third of the variation in spatial ability at age 12 is explained by genetic factors; a little less than half of the variation in mathematics at this age is genetic.
We find no sex differences in the genetic and environmental influences (either in magnitude or type) on mathematical and spatial variation at age 12.
The observed overlap between spatial ability and mathematics is substantial (r > .40). Approximately 60% of this overlap is explained by common genetic effects, with 40% of the overlap due to environmental experience.
Spatial ability predicts performance in mathematics and eventual expertise in science, technology and engineering. Spatial skills have been shown to rely on neuronal networks partially shared with mathematics. The results of this study suggest that ∼60% of the observed covariation between the two traits is due to common genetic factors, the environmental contribution is ∼40%. Understanding the nature of this association and identifying environmental mediators of the spatial‐mathematics relationship can inform educational practices and intervention for mathematical underperformance.
Obesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the ...causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue.
To investigate whether higher BMI increases the risk of major depression.
Two instrumental variable analyses were conducted to test the causal relationship between obesity and major depression in RADIANT, a large case-control study of major depression. We used a single nucleotide polymorphism (SNP) in FTO and a genetic risk score (GRS) based on 32 SNPs with well-established associations with BMI.
Linear regression analysis, as expected, showed that individuals carrying more risk alleles of FTO or having higher score of GRS had a higher BMI. Probit regression suggested that higher BMI is associated with increased risk of major depression. However, our two instrumental variable analyses did not support a causal relationship between higher BMI and major depression (FTO genotype: coefficient -0.03, 95% CI -0.18 to 0.13, P = 0.73; GRS: coefficient -0.02, 95% CI -0.11 to 0.07, P = 0.62).
Our instrumental variable analyses did not support a causal relationship between higher BMI and major depression. The positive associations of higher BMI with major depression in probit regression analyses might be explained by reverse causality and/or residual confounding.
Chaotic homes and school achievement: a twin study Hanscombe, Ken B.; Haworth, Claire M.A.; Davis, Oliver S.P. ...
Journal of child psychology and psychiatry,
November 2011, Letnik:
52, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Background: Chaotic homes predict poor school performance. Given that it is known that genes affect both children’s experience of household chaos and their school achievement, to what extent is the ...relationship between high levels of noise and environmental confusion in the home, and children’s school performance, mediated by heritable child effects? This is the first study to explore the genetic and environmental pathways between household chaos and academic performance.
Method: Children’s perceptions of family chaos at ages 9 and 12 and their school performance at age 12 were assessed in more than 2,300 twin pairs. The use of child‐specific measures in a multivariate genetic analysis made it possible to investigate the genetic and environmental origins of the covariation between children’s experience of chaos in the home and their school achievement.
Results: Children’s experience of family chaos and their school achievement were significantly correlated in the expected negative direction (r = −.26). As expected, shared environmental factors explained a large proportion (63%) of the association. However, genetic factors accounted for a significant proportion (37%) of the association between children’s experience of household chaos and their school performance.
Conclusions: The association between chaotic homes and poor performance in school, previously assumed to be entirely environmental in origin, is in fact partly genetic. How children’s home environment affects their academic achievement is not simply in the direction environment → child → outcome. Instead, genetic factors that influence children’s experience of the disordered home environment also affect how well they do at school. The relationship between the child, their environment and their performance at school is complex: both genetic and environmental factors play a role.
For nearly a century, twin and adoption studies have yielded substantial estimates of heritability for cognitive abilities, although it has proved difficult for genomewide-association studies to ...identify the genetic variants that account for this heritability (i.e., the missing-heritability problem). However, a new approach, genomewide complex-trait analysis (GCTA), forgoes the identification of individual variants to estimate the total heritability captured by common DNA markers on genotyping arrays. In the same sample of 3,154 pairs of 12-year-old twins, we directly compared twin-study heritability estimates for cognitive abilities (language, verbal, nonverbal, and general) with GCTA estimates captured by 1.7 million DNA markers. We found that DNA markers tagged by the array accounted for .66 of the estimated heritability, reaffirming that cognitive abilities are heritable. Larger sample sizes alone will be sufficient to identify many of the genetic variants that influence cognitive abilities.
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