Assessing individual differences in genome-wide gene expression in human whole blood: reliability over four hours and stability over 10 months.

Studying the causes and correlates of natural variation in gene expression in healthy populations assumes that individual differences in gene expression can be reliably and stably assessed across time. However, this is yet to be established. We examined 4-hour test-retest reliability and 10 month test-retest stability of individual differences in gene expression in ten 12-year-old children. Blood was collected on four occasions: 10 a.m. and 2 p.m. on Day 1 and 10 months later at 10 a.m. and 2 p.m. Total RNA was hybridized to Affymetrix-U133 plus 2.0 arrays. For each probeset, the correlation across individuals between 10 a.m. and 2 p.m. on Day 1 estimates test-retest reliability. We identified 3,414 variable and abundantly expressed probesets whose 4-hour test-retest reliability exceeded .70, a conventionally accepted level of reliability, which we had 80% power to detect. Of the 3,414 reliable probesets, 1,752 were also significantly reliable 10 months later. We assessed the long-term stability of individual differences in gene expression by correlating the average expression level for each probe-set across the two 4-hour assessments on Day 1 with the average level of each probe-set across the two 4-hour assessments 10 months later. 1,291 (73.7%) of the 1,752 probe-sets that reliably detected individual differences across 4 hours on two occasions, 10 months apart, also stably detected individual differences across 10 months. Heritability, as estimated from the MZ twin intraclass correlations, is twice as high for the 1,752 reliable probesets versus all present probesets on the array (0.68 vs 0.34), and is even higher (0.76) for the 1,291 reliable probesets that are also stable across 10 months. The 1,291 probesets that reliably detect individual differences from a single peripheral blood collection and stably detect individual differences over 10 months are promising targets for research on the causes (e.g., eQTLs) and correlates (e.g., psychopathology) of individual differences in gene expression

Genome-wide association study of receptive language ability of 12 year olds

Purpose: We have previously shown that individual differences in measures of receptive language ability at age 12 are highly heritable. The current study attempted to identify some of the genes responsible for the heritability of receptive language ability using a genome-wide association (GWA) approach. Method: We administered four internet-based measures of receptive language (vocabulary, semantics, syntax, and pragmatics) to a sample of 2329 12-year-olds for whom DNA and genome-wide genotyping were available. Nearly 700,000 single-nucleotide polymorphisms (SNPs) and one million imputed SNPs were included in a GWA analysis of receptive language composite scores. Results: No SNP associations met the demanding criterion of genome-wide significance that corrects for multiple testing across the genome (p < 5 ×10-8). The strongest SNP association did not replicate in an additional sample of 2639 12-year-olds. Conclusion: These results indicate that individual differences in receptive language ability in the general population do not reflect common genetic variants that account for >3% of the phenotypic variance. The search for genetic variants associated with language skill will require larger samples and additional methods to identify and functionally characterize the full spectrum of risk variants

Common aetiology for diverse language skills in 41/2-year-old twins

Multivariate genetic analysis was used to examine the genetic and environmental aetiology of the interrelationships of diverse linguistic skills. This study used data from a large sample of 4 1/2 year-old twins who were tested on measures assessing articulation, phonology, grammar, vocabulary, and verbal memory. Phenotypic analysis suggested two latent factors: articulation (2 measures) and general language (the remaining 7), and a genetic model incorporating these factors provided a good fit to the data. Almost all genetic and shared environmental influences on the 9 measures acted through the two latent factors. There was also substantial aetiological overlap between the two latent factors, with a genetic correlation of 0·64 and shared environment correlation of 1·00. We conclude that to a large extent, the same genetic and environmental factors underlie the development of individual differences in a wide range of linguistic skills

Genetics and Genomics: Good, bad and ugly

The chapter considers the importance and potential contributions of genetics to education and to neuroscience in education (good), the general view about genetics in education (bad), and attempts to date to identify specific genes throughout the genome responsible for ubiquitous genetic influence (ugly). We will use as an example of research one topic of great importance to education – variation in mathematical ability and achievement -- to illustrate the main points

Genetic, environmental and gender influences on attachment disorder behaviours

Background Despite current interest in attachment disorder, there is concern about its discrimination from other disorders and an unproven assumption of an environmental aetiology. Aims To test whether behaviours suggestive of attachment disorder are distinct from other childhood behavioural and emotional problems and are solely environmentally determined. Method In a community sample of 13 472 twins, we carried out factor analysis of questionnaire items encompassing behaviours indicative of attachment disorder, conduct problems, hyperactivity and emotional difficulties. We used behavioural genetic model-fitting analysis to explore the contribution of genes and environment. Results Factor analysis showed clear discrimination between behaviours suggestive of attachment disorder, conduct problems, hyperactivity and emotional problems. Behavioural genetics analysis suggested a strong genetic influence to attachment disorder behaviour, with males showing higher heritability. Conclusions Behaviours suggestive of attachment disorder can be differentiated from common childhood emotional and behavioural problems and appear to be strongly genetically influenced, particularly in boys. INTRODUCTION TOP ABSTRACT INTRODUCTION METHOD RESULTS DISCUSSION REFERENCES There have been recent attempts to codify behaviours associated with early neglect and institutionalisation (Chisolm et al, 1995; Zeanah et al, 2004) into a psychiatric category. Both DSM–IV and ICD–10 describe reactive attachment disorder, with two subtypes encompassing inhibited and disinhibited behaviour (World Health Organization, 1992; American Psychiatric Association, 1994). Questions remain about the nosology of the syndrome beyond age 5 years (American Academy of Child and Adolescent Psychiatry, 2005), therefore we simply refer to ‘attachment disorder behaviours’. We seek to extend the extant literature by testing two hypotheses: first, that the two subtypes are distinct from one another and from other common behavioural and emotional problems in young children, and second that these behavioural patterns are environmentally mediated. We capitalise on a twin study, a design that provides particular leverage in testing environmental hypotheses

Common DNA markers can account for more than half of the genetic influence on cognitive abilities

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

Angry responses to infant challenges: parent, marital, and child genetic factors associated with harsh parenting

This study examined genetic and environmental influences on harsh parenting of 9-month-olds. We examined whether positive child-, parent-, and family-level characteristics were associated with harsh parenting in addition to negative characteristics. We were particularly interested in examining evocative gene-environment correlation (rGE) by testing the effect of birth parent temperament on adoptive parents’ harsh parenting. Additionally, we examined associations among adoptive parents’ own temperaments, their marital relationship quality, and harsh parenting. Adoptive fathers’ (but not adoptive mothers’) harsh parenting was inversely related to an index of birth mother positive temperament (reward dependence), indicating evocative rGE. Higher marital quality was associated with less harsh parenting, but only for adoptive fathers. Adoptive parents’ negative temperamental characteristics (harm avoidance) were related to hostile parenting. Findings suggest the importance of enhancing positive family characteristics in addition to mitigating negative characteristics, as well as engaging multiple levels of the family system to prevent harsh parenting. Children have the potential to evoke strong positive and negative affective responses from parents, which then influence and organize caregiving behavior (Dix, 1991). All young children demonstrate challenging behaviors, such as prolonged crying that may be difficult to soothe, uncooperativeness with bathing or dressing, or difficulty with eating or sleeping. The degree to which parental negative emotion is evoked by these challenges and expressed in interactions with children is often characterized as harsh or overreactive parenting. Harsh parenting is a function of a complex interplay of risk and protective factors that operate at multiple levels of the family system (i.e., characteristics of the parent, child, and family environment; Belsky, 1984; Boivin et al., 2005; DiLalla & Bishop, 1996; Neiderhiser et al., 2004, 2007; Towers, Spotts, & Neiderhiser, 2002). The long-term maladaptive developmental outcomes associated with harsh, negative parenting during infancy (Bayer, Ukoumunne, Mathers, Wake, Abdi, & Hiscock, 2012; Bradley & Corwyn, 2008; Lorber & Egeland, 2009) underscore the need for improved understanding of risk and protective factors associated with early harsh parenting. The current study aims to extend on the research on harsh parenting in infancy in two ways. First, although risk factors for early harsh parenting are well documented, we know little about factors that buffer parents from harsh parenting during infancy; this study examines independent and differential effects of positive and negative characteristics on harsh parenting. Second, although interest in child effects on parenting, including harsh parenting, has been present in the field for decades (Bell, 1979; Bell & Chapman, 1986; Rutter et al., 1997) we know very little about the degree to which the effects found in the literature truly reflect evocative effects of infants’ genetically influenced characteristics. The current study used an adoption design to test the hypothesis that genetically influenced temperamental characteristics of 9-month-olds would influence adoptive parents’ harsh parenting. Previous research has identified many correlates of harsh parenting, including negative characteristics of the parent (e.g., maternal depression; Lovejoy, Graczyk, O’Hare, & Neuman, 2000), family (e.g., marital hostility, Rhoades et al., 2011), and child (e.g., difficult temperament, Plomin, Loehlin & DeFries, 1985; poor regulation, Bridgett et al., 2009). Previous research has identified risk factors for harsh parenting, but very little is known about how positive parent, child, and family characteristics might mitigate it. For example, a positive marital relationship could buffer the impact of high levels of depressive symptoms on parenting, and thus have implications for prevention and intervention efforts. The current study examined positive and negative parent, child, and family factors in association with harsh parenting. A second emphasis centered on understanding the role of infants’ genetically influenced characteristics on harsh parenting. Much of the previous work on child effects on parenting has examined child temperament. In general, child positivity is related to positive parenting, while child negativity is related to negative parenting (Putnam, Sanson, & Rothbart, 2002; Wilson & Durbin, 2012). However, the general lack of genetically sensitive designs in this research makes it impossible to determine whether these associations exist because (1) harsh parenting leads to negative child characteristics, (2) specific child characteristics evoke harsh parenting (evocative gene-environment correlation, rGE; Plomin, Loehlin & DeFries, 1977; Scarr & McCartney, 1983) or (3) children and parents share genes that contribute to both parenting and temperament (passive gene-environment correlation). Therefore, genetically-sensitive research designs are needed to disentangle these influences to understand specific mechanisms underlying relations between child characteristics and parent behavior

Does private education make nicer people? The influence of school type on social–emotional development

In a longitudinal sample from Britain, we tested if attending private, fee-charging schools rather than non-selective state schools benefitted children’s social–emotional development. State (N = 2,413) and private school children (N = 269) showed no differences in well-being across adolescence, but private school children reported fewer behaviour problems and greater peer victimisation over time than state schoolers. These results were independent of schools’ selection criteria, including family background, and prior academic and cognitive performance. At age 21, private and state school students differed marginally in social–emotional behaviours, such as self-control, volunteering, sexual conduct, and substance use. After considering schools’ selection criteria, only risk taking and age at having the first alcoholic drink differed between private and state school children, with the privately educated ones being less risk averse and drinking at younger ages than those attending state school. Our results suggest that private education adds little positive value to children’s social–emotional development