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

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

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 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

Exploring the association between anxiety and conduct problems in a large sample of twins aged 2-4

Anxiety and conduct problems covary, yet studies have not explored the genetic and environmental origins of this association.We analyzed parent-reported anxiety and conduct problems in 6,783 pairs of twins at 2-, 3-, and 4-years of age. As anxiety and conduct problems were fairly stable across the three ages (average 1-year correlation was .53), ratings from all three were combined. The aggregate anxiety and conduct ratings correlated .33 for boys and .30 for girls. Bivariate genetic analyses indicated fairly low genetic correlations (.31 for boys, .16 for girls), and high shared environmental correlations (1.0 for boys and 0.99 for girls) between anxiety and conduct problems. Most of the phenotypic correlation was accounted for by shared environmental mediation (65% for boys and 94% for girls), indicating that many of the same family environmental factors are responsible for the development of both anxiety and conduct problems

Do MZ twins have discordant experiences of friendship? : A qualitative hypothesis-generating MZ twin differences study

[This corrects the article DOI: 10.1371/journal.pone.0180521.]

A shared genetic propensity underlies experiences of bullying victimization in late childhood and self-rated paranoid thinking in adolescence

Background: Bullying is a risk factor for developing psychotic experiences (PEs). Whether bullying is associated with particular PEs, and the extent to which genes and environments influence the association, are unknown. This study investigated which specific PEs in adolescence are associated with earlier bullying victimization and the genetic and environmental contributions underlying their association. Method: Participants were 4826 twin pairs from a longitudinal community-based twin study in England and Wales who reported on their bullying victimization at the age of 12 years. Measures of specific PEs (self-rated Paranoia, Hallucinations, Cognitive disorganization, Grandiosity, Anhedonia, and parent-rated Negative Symptoms) were recorded at age of 16 years. Results: Childhood bullying victimization was most strongly associated with Paranoia in adolescence (r = .26; P < .01), with weaker associations with Hallucinations, Cognitive Disorganization, parent-rated Negative Symptoms (r = .12–.20; P < .01), Grandiosity (r = .04; P < .05), and Anhedonia (r = .00, n.s.). Bivariate twin model-fitting demonstrated that bullying victimization and Paranoia were both heritable (35% and 52%, respectively) with unique environmental influences (39% and 48%, respectively), and bullying victimization showed common environmental influences (26%). The association between bullying victimization and Paranoia operated almost entirely via genetic influences (bivariate heritability = 93%), with considerable genetic overlap (genetic correlation = .55). Conclusion: In contrast to the assumed role of bullying victimization as an environmental trigger, these data suggest that bullying victimization in late childhood is particularly linked to self-rated Paranoia in adolescence via a shared genetic propensity. Clinically, individuals with a history of bullying victimization are predicted to be particularly susceptible to paranoid symptoms