Why are children in the same family so different from one another?

One of the most important findings that has emerged from human behavioral genetics involves the environment rather than heredity, providing the best available evidence for the importance of environmental influences on personality, psychopathology, and cognition. The research also converges on the remarkable conclusion that these environmental influences make two children in the same family as different from one another as are pairs of children selected randomly from the population. The theme of the target article is that environmental differences between children in the same family (called "nonshared environment") represent the major source of environmental variance for personality, psychopathology, and cognitive abilities.

Stable genetic influence on anxiety-related behaviours across middle childhood.

We examined the aetiology of anxiety symptoms in an unselected population at ages 7 and 9, a period during which anxiety disorders first begin to develop (mean age at onset is 11 years). Specifically, the aim of the study was to investigate genetic and environmental continuity and change in components of anxiety in middle childhood. Parents of over 3,500 twin pairs completed the Anxiety-Related Behaviours Questionnaire (ARBQ) when twins were 7 and 9 years old.

Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility.

Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals.

Chaotic homes and school achievement: a twin study.

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 nature (and nurture) of children's perceptions of family chaos.

Chaos in the home is a key environment in cognitive and behavioral development. However, we show that children's experience of home chaos is partly genetically mediated. We assessed children's perceptions of household chaos at ages 9 and 12 in 2337 pairs of twins.

A longitudinal twin study on the association between inattentive and hyperactive-impulsive ADHD symptoms.

DSM-IV distinguishes two symptom domains of attention deficit hyperactivity disorder (ADHD): inattentiveness and hyperactivity-impulsivity. The present study examines the aetiologies and developmental relations underlying the associations between inattentiveness and hyperactivity-impulsivity over time, based on a representative population sample from the United Kingdom of approximately 7,000 twin pairs. ADHD symptoms were assessed as continuous dimensions using the DSM-IV items from the Conners' Parent Rating Scale at two ages: middle childhood (age 1) and early adolescence (age 2).

A twin study of ADHD symptoms in early adolescence: hyperactivity-impulsivity and inattentiveness show substantial genetic overlap but also genetic specificity.

A previous paper in this journal revealed substantial genetic overlap between the ADHD dimensions of hyperactivity-impulsivity and inattentiveness in a sample of 8-year old twins drawn from a UK-representative population sample. Four years later, when the twins were 12 years old, more than 5,500 pairs drawn from the same sample were rated again on the DSM-IV based Revised Conners' Parent Rating Scale to assess symptoms on both ADHD dimensions. Heritabilities were high (around 70%) for both hyperactivity-impulsivity and inattentiveness and evidence for etiological sex differences was absent.

Added value measures in education show genetic as well as environmental influence.

Does achievement independent of ability or previous attainment provide a purer measure of the added value of school? In a study of 4000 pairs of 12-year-old twins in the UK, we measured achievement with year-long teacher assessments as well as tests. Raw achievement shows moderate heritability (about 50%) and modest shared environmental influences (25%). Unexpectedly, we show that for indices of the added value of school, genetic influences remain moderate (around 50%), and the shared (school) environment is less important (about 12%).

Genetic Overlap between ADHD Symptoms and Reading is largely Driven by Inattentiveness rather than Hyperactivity-Impulsivity.

Objective: To assess the genetic and environmental etiology of the co-occurence of ADHD symptoms and reading difficulties using the largest sample to date, distinguishing two dimensions of ADHD and two of reading.

Method: Data were obtained from 6428 12-year old twin pairs drawn from the population-based Twins Early Development Study. ADHD symptoms (combined ADHD, inattentiveness and hyperactivity-impulsivity) were assessed using parent ratings.

Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes.

Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.

Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21.

We performed a genome-wide association study (GWAS) in 1705 Parkinson's disease (PD) UK patients and 5175 UK controls, the largest sample size so far for a PD GWAS. Replication was attempted in an additional cohort of 1039 French PD cases and 1984 controls for the 27 regions showing the strongest evidence of association (P< 10(-4)). We replicated published associations in the 4q22/SNCA and 17q21/MAPT chromosome regions (P< 10(-10)) and found evidence for an additional independent association in 4q22/SNCA.

Gene-environment interaction in the etiology of mathematical ability using SNP sets.

Mathematics ability and disability is as heritable as other cognitive abilities and disabilities, however its genetic etiology has received relatively little attention. In our recent genome-wide association study of mathematical ability in 10-year-old children, 10 SNP associations were nominated from scans of pooled DNA and validated in an individually genotyped sample. In this paper, we use a 'SNP set' composite of these 10 SNPs to investigate gene-environment (GE) interaction, examining whether the association between the 10-SNP set and mathematical ability differs as a function of ten environmental measures in the home and school in a sample of 1888 children with complete data.

A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.

To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2).

A novel approach to genetic and environmental analysis of cross-lagged associations over time: the cross-lagged relationship between self-perceived abilities and school achievement is mediated by genes as well as the environment.

Using longitudinal cross-lagged analysis to infer causal directions of reciprocal effects is one of the most important tools in the developmental armamentarium. The strength of these analyses can be enhanced by analyzing the genetic and environmental aetiology underlying cross-lagged relationships, for which we present a novel approach here. Our approach is based on standard Cholesky decomposition.

Genetics and Intervention Research.

As part of this special section on genetics and behavioral intervention, we discuss the articles by McGue, Osler, and Christensen (2010, this issue) and by Davey Smith (2010, this issue). In the second half of the present article, we consider the integration of genetics and intervention research more broadly. The two articles describe ways to use genetic controls to infer causation from correlational ("observational") data without intervention.

Quantitative genetics in the era of molecular genetics: learning abilities and disabilities as an example.

Objective: To consider recent findings from quantitative genetic research in the context of molecular genetic research, especially genome-wide association studies. We focus on findings that go beyond merely estimating heritability. We use learning abilities and disabilities as examples.

The etiology of diverse receptive language skills at 12 years.

Purpose: In the 2nd decade of life, language skills expand in both quantitative and qualitative ways. The etiology of these new skills and the relationships among them have been little explored.

Method: Taking advantage of widespread access to inexpensive and fast Internet connections in the United Kingdom, we administered four Web-based measures of receptive language development--Vocabulary, Listening Grammar, Figurative Language, and Making Inferences--to a sample of 12-year-old twin pairs (N=4,892) participating in the Twins Early Development Study (TEDS; Oliver & Plomin, 2007).

Generalist genes analysis of DNA markers associated with mathematical ability and disability reveals shared influence across ages and abilities.

Background: The Generalist Genes Hypothesis is based upon quantitative genetic findings which indicate that many of the same genes influence diverse cognitive abilities and disabilities across age. In a recent genome-wide association study of mathematical ability in 10-year-old children, 43 SNP associations were nominated from scans of pooled DNA, 10 of which were validated in an individually genotyped sample. The 4927 children in this genotyped sample have also been studied at 7, 9 and 12 years of age on measures of mathematical ability, as well as on other cognitive and learning abilities.

DNA methylation profiling using bisulfite-based epityping of pooled genomic DNA.

DNA methylation plays a vital role in normal cellular function, with aberrant methylation signatures being implicated in a growing number of human pathologies and complex human traits. Methods based on the modification of genomic DNA with sodium bisulfite are considered the 'gold-standard' for DNA methylation profiling on genomic DNA; however they require large amounts of DNA and may be prohibitively expensive when used on the large sample sizes necessary to detect small effects. DNA pooling approaches are already widely used in large-scale studies of DNA sequence and gene expression.

More than just IQ: A longitudinal examination of self-perceived abilities as predictors of academic performance in a large sample of UK twins.

This paper examines the longitudinal causal relationship between self-perceived abilities (SPA) and academic achievement (Ach) while controlling for cognitive ability (CA). In all, 5957 UK school children were assessed on SPA, Ach and CA at ages 9 and 12. Results indicated that SPA and Ach at age 9 independently affected both SPA and Ach at age 12, even when CA was considered.

Visualizing genetic similarity at the symptom level: the example of learning disabilities.

Psychological traits and disorders are often interrelated through shared genetic influences. A combination of maximum-likelihood structural equation modelling and multidimensional scaling enables us to open a window onto the genetic architecture at the symptom level, rather than at the level of latent genetic factors. We illustrate this approach using a study of cognitive abilities involving over 5,000 pairs of twins.

Two by two: a twin study of second-language acquisition.

In this report, we provide initial results of the first application of the classic twin design to second-language acquisition. The analysis was conducted on assessments teachers made using United Kingdom National Curriculum standards and included 604 pairs of 14-year-old twins. The results demonstrate substantial heritability (.

Preschool speech, language skills, and reading at 7, 9, and 10 years: etiology of the relationship.

Purpose: To examine the etiology of the relationship between preschool speech and language, and later reading skills.

Method: One thousand six hundred seventy-two children from the Twins Early Development Study (B. R.

Genetics of learning abilities and disabilities: recent developments from the UK and possible directions for research in China. 2008.

It is exciting to witness the birth of behavioral genetics in China at a time when the field of genetics is exploding with new discoveries. We begin by discussing the potential for Chinese researchers to sidestep the false starts of previous genetic research on behavior and to become leaders rather than followers in behavioral genetics research. Using learning abilities and disabilities as an example, the rest of the paper considers ways in which quantitative genetic research can go beyond the nature versus nurture question to ask more interesting questions about genetics and psychology.