The classical twin study is the most popular design in behavioural genetics. It has strong roots in biometrical genetic theory, which allows predictions to be made about the correlations between observed traits of identical and fraternal twins in terms of underlying genetic and environmental components. One can infer the relative importance of these 'latent' factors (model parameters) by structural equation modelling (SEM) of observed covariances of both twin types. SEM programs estimate model parameters by minimising a goodness-of-fit function between observed and predicted covariance matrices, usually by the maximum-likelihood criterion. Likelihood ratio statistics also allow the comparison of fit of different competing models. The program Mx, specifically developed to model genetically sensitive data, is now widely used in twin analyses. The flexibility of Mx allows the modelling of multivariate data to examine the genetic and environmental relations between two or more phenotypes and the modelling to categorical traits under liability-threshold models.

As defined by the DSM-IV, BPD is highly heritable. There are substantial genetic and nonshared environmental correlations between mania and depression, but most of the genetic variance in liability to mania is specific to the manic syndrome.

BackgroundThe etiology of Autism Spectrum Disorder (ASD) has been recently debated due to emerging findings on the importance of shared environmental influences. However, two recent twin studies do not support this and instead re‐affirm strong genetic effects on the liability to ASD, a finding consistent with previous reports. This study conducts a systematic review and meta‐analysis of all twin studies of ASD published to date and explores the etiology along the continuum of a quantitative measure of ASD.MethodsA PubMed Central, Science Direct, Google Scholar, Web of Knowledge structured search conducted online, to identify all twin studies on ASD published to date. Thirteen primary twin studies were identified, seven were included in the meta‐analysis by meeting Systematic Recruitment criterion; correction for selection and ascertainment strategies, and applied prevalences were assessed for these studies. In addition, a quantile DF extremes analysis was carried out on Childhood Autism Spectrum Test scores measured in a population sample of 6,413 twin pairs including affected twins.ResultsThe meta‐analysis correlations for monozygotic twins (MZ) were almost perfect at .98 (95% Confidence Interval, .96–.99). The dizygotic (DZ) correlation, however, was .53 (95% CI .44–.60) when ASD prevalence rate was set at 5% (in line with the Broad Phenotype of ASD) and increased to .67 (95% CI .61–.72) when applying a prevalence rate of 1%. The meta‐analytic heritability estimates were substantial: 64–91%. Shared environmental effects became significant as the prevalence rate decreased from 5–1%: 07–35%. The DF analyses show that for the most part, there is no departure from linearity in heritability.ConclusionsWe demonstrate that: (a) ASD is due to strong genetic effects; (b) shared environmental effects become significant as a function of lower prevalence rate; (c) previously reported significant shared environmental influences are likely a statistical artefact of overinclusion of concordant DZ twins.

Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and alpha-2-macroglobulin (alpha-2M). Using semi-quantitative immunoblotting, the elevation of CFH and alpha-2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as alpha-2M may be a specific markers of this illness.

Causal inference is essential across the biomedical, behavioural and social sciences.By progressing from confounded statistical associations to evidence of causal relationships, causal inference can reveal complex pathways underlying traits and diseases and help to prioritize targets for intervention. Recent progress in genetic epidemiology - including statistical innovation, massive genotyped data sets and novel computational tools for deep data mining - has fostered the intense development of methods exploiting genetic data and relatedness to strengthen causal inference in observational research. In this Review, we describe how such genetically informed methods differ in their rationale, applicability and inherent limitations and outline how they should be integrated in the future to offer a rich causal inference toolbox.

If diagnostic hierarchies are relaxed, there is a degree of overlap in the genes contributing to RDC schizophrenic, schizoaffective, and manic syndromes. Supplementing the traditional approach of assigning a single main lifetime diagnosis with information on within-person comorbidity of psychotic syndromes may provide valuable information about the familial aggregation of psychotic symptoms.

IMPORTANCE Most evidence to date highlights the importance of genetic influences on the liability to autism and related traits. However, most of these findings are derived from clinically ascertained samples, possibly missing individuals with subtler manifestations, and obtained estimates may not be representative of the population. OBJECTIVES To establish the relative contributions of genetic and environmental factors in liability to autism spectrum disorder (ASD) and a broader autism phenotype in a large population-based twin sample and to ascertain the genetic/environmental relationship between dimensional trait measures and categorical diagnostic constructs of ASD. DESIGN, SETTING, AND PARTICIPANTS We used data from the population-based cohort Twins Early Development Study, which included all twin pairs born in England and Wales from January 1, 1994, through December 31, 1996. We performed joint continuous-ordinal liability threshold model fitting using the full information maximum likelihood method to estimate genetic and environmental parameters of covariance. Twin pairs underwent the following assessments: the Childhood Autism Spectrum Test (CAST) (6423 pairs; mean age, 7.9 years), the Development and Well-being Assessment (DAWBA) (359 pairs; mean age, 10.3 years), the Autism Diagnostic Observation Schedule (ADOS) (203 pairs; mean age, 13.2 years), the Autism Diagnostic Interview–Revised (ADI-R) (205 pairs; mean age, 13.2 years), and a best-estimate diagnosis (207 pairs). MAIN OUTCOMES AND MEASURES Participants underwent screening using a population-based measure of autistic traits (CAST assessment), structured diagnostic assessments (DAWBA, ADI-R, and ADOS), and a best-estimate diagnosis. RESULTS On all ASD measures, correlations among monozygotic twins (range, 0.77-0.99) were significantly higher than those for dizygotic twins (range, 0.22-0.65), giving heritability estimates of 56% to 95%. The covariance of CAST and ASD diagnostic status (DAWBA, ADOS and best-estimate diagnosis) was largely explained by additive genetic factors (76%-95%). For the ADI-R only, shared environmental influences were significant (30% [95% CI, 8%-47%]) but smaller than genetic influences (56% [95% CI, 37%-82%]). CONCLUSIONS AND RELEVANCE The liability to ASD and a more broadly defined high-level autism trait phenotype in this large population-based twin sample derives primarily from additive genetic and, to a lesser extent, nonshared environmental effects. The largely consistent results across different diagnostic tools suggest that the results are generalizable across multiple measures and assessment methods. Genetic factors underpinning individual differences in autismlike traits show considerable overlap with genetic influences on diagnosed ASD.

This study examined the direction and etiology underlying the relationships between parental negativity and early childhood antisocial behavior using a bidirectional effects model in a longitudinal genetically informative design. We analyzed parent reports of parental negativity and early childhood antisocial behavior in 6,230 pairs of twins at 4 and 7 years of age. Results from a cross-lagged twin model contribute to the understanding of the mechanisms underlying the bidirectional processes involved in parental negativity and childhood antisocial behavior. Specifically, the findings of this study suggest that the association between parenting and child antisocial behavior is best explained by both parent-driven and child-driven effects. We found support for the notion that parent's negative feelings towards their children environmentally mediate the risk for child antisocial behavior. We also found evidence of genetically mediated child effects; in which genetically influenced antisocial behavior evoke parental negativity towards the child.