Unidirectional and bidirectional causation between smoking and blood DNA methylation: evidence from twin-based Mendelian randomisation.

Cigarette smoking is associated with numerous differentially-methylated genomic loci in multiple human tissues. These associations are often assumed to reflect the causal effects of smoking on DNA methylation (DNAm), which may underpin some of the adverse health sequelae of smoking. However, prior causal analyses with Mendelian Randomisation (MR) have found limited support for such effects.

On the Detection of Population Heterogeneity in Causation Between Two Variables: Finite Mixture Modeling of Data Collected from Twin Pairs.

Causal inference is inherently complex and relies on key assumptions that can be difficult to validate. One strong assumption is population homogeneity, which assumes that the causal direction remains consistent across individuals. However, there may be variation in causal directions across subpopulations, leading to potential heterogeneity.

On the detection of population heterogeneity in causation between two variables: Finite mixture modeling of data collected from twin pairs.

Causal inference is inherently complex, often dependent on key assumptions that are sometimes overlooked. One such assumption is the potential for unidirectional or bidirectional causality, while another is population homogeneity, which suggests that the causal direction between two variables remains consistent across the study sample. Discerning these processes requires meticulous data collection through an appropriate research design and the use of suitable software to define and fit alternative models.

Unidirectional and Bidirectional Causation between Smoking and Blood DNA Methylation: Evidence from Twin-based Mendelian Randomisation.

Cigarette smoking is associated with numerous differentially-methylated genomic loci in multiple human tissues. These associations are often assumed to reflect the causal effects of smoking on DNA methylation (DNAm), which may underpin some of the adverse health sequelae of smoking. However, prior causal analyses with Mendelian Randomisation (MR) have found limited support for such effects.

Using Instrumental Variables to Measure Causation over Time in Cross-Lagged Panel Models.

Cross-lagged panel models (CLPMs) are commonly used to estimate causal influences between two variables with repeated assessments. The lagged effects in a CLPM depend on the time interval between assessments, eventually becoming undetectable at longer intervals. To address this limitation, we incorporate instrumental variables (IVs) into the CLPM with two study waves and two variables.

Are Genetic and Environmental Risk Factors for Psychopathology Amplified in Children with Below-Average Intelligence? A Population-Based Twin Study.

There is a negative association between intelligence and psychopathology. We analyzed data on intelligence and psychopathology to assess this association in seven-year-old Dutch twin pairs (ranging from 616 to 14,150 depending on the phenotype) and estimated the degree to which genetic and environmental factors common to intelligence and psychopathology explain the association. Secondly, we examined whether genetic and environmental effects on psychopathology are moderated by intelligence.

The relationship of school performance with self-control and grit is strongly genetic and weakly causal.

The non-cognitive skills self-control and grit are often considered predictors of school performance, but whether this relationship is causal remains unclear. We investigated the causality of this association using a twin design. Specifically, we evaluated the direct impact of self-control and grit on school performance, while controlling for genetic or environmental influences common to all three traits (i.

Power, measurement error, and pleiotropy robustness in twin-design extensions to Mendelian Randomization.

Mendelian Randomization (MR) has become an important tool for causal inference in the health sciences. It takes advantage of the random segregation of alleles to control for background confounding factors. In brief, the method works by using genetic variants as instrumental variables, but it depends on the assumption of exclusion restriction, i.

Self-control and grit are associated with school performance mainly because of shared genetic effects.

Background: By combining the classical twin design with regression analysis, we investigated the role of two non-cognitive factors, self-control and grit, in the prediction of school performance. We did so at the phenotypic, genetic, and environmental level.

Methods: Teachers filled out a survey on the twins' school performance (school grades for reading, literacy, and math), self-control (ASEBA self-control scale), and grit (the perseverance aspect) for 4891 Dutch 12-years-old twin pairs (3837 pairs with data for both and 1054 pairs with data for one of the twins).

Handedness and 23 Early Life Characteristics in 37,495 Dutch Twins.

In studies of singletons, a range of early-life characteristics have been reported to be associated with handedness, but some of these associations have failed to replicate. We examined associations between 23 early life characteristics with handedness in a large sample of 37,495 5-year-old twins. We considered three definitions of handedness: left-handedness (LH), mixed-handedness (MH), and non-right-handedness (NRH).

The mechanism of assortative mating for educational attainment: a study of Finnish and Dutch twins and their spouses.

Assortative mating refers describes a phenomenon in which individuals with similar phenotypic traits are more likely to mate and reproduce with each other; i.e. assortative mating occurs when individuals choose partners based on their similarity or dissimilarity in certain traits.

Interpretational issues with the bifactor model: a commentary on 'Defining the -Factor: An Empirical Test of Five Leading Theories' by Southward, Cheavens, and Coccaro.

Southward, Cheavens, and Coccaro (2022, ) conducted an ambitious investigation aimed at determining the nature of the general factor of psychopathology by considering the correlation between the factor and five candidate constructs. Generally, in this area of research, the bifactor model is preferred to the second order common factor model. In this commentary, we identify several interpretational issues concerning the bifactor model, which are based on a realistic psychometric view of latent variables.

Language and reading impairments are associated with increased prevalence of non-right-handedness.

Handedness has been studied for association with language-related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non-right-handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex-matched controls identified from 10 distinct cohorts (age range 6-19 years old; European ethnicity) using a priori set criteria.

MR-DoC2: Bidirectional Causal Modeling with Instrumental Variables and Data from Relatives.

Establishing causality is an essential step towards developing interventions for psychiatric disorders, substance use and many other conditions. While randomized controlled trials (RCTs) are considered the gold standard for causal inference, they are unethical in many scenarios. Mendelian randomization (MR) can be used in such cases, but importantly both RCTs and MR assume unidirectional causality.

Gene-environment correlations across geographic regions affect genome-wide association studies.

Gene-environment correlations affect associations between genetic variants and complex traits in genome-wide association studies (GWASs). Here we showed in up to 43,516 British siblings that educational attainment polygenic scores capture gene-environment correlations, and that migration extends these gene-environment correlations beyond the family to broader geographic regions. We then ran GWASs on 56 complex traits in up to 254,387 British individuals.

The heritability of vocal tract structures estimated from structural MRI in a large cohort of Dutch twins.

While language is expressed in multiple modalities, including sign, writing, or whistles, speech is arguably the most common. The human vocal tract is capable of producing the bewildering diversity of the 7000 or so currently spoken languages, but relatively little is known about its genetic bases, especially in what concerns normal variation. Here, we capitalize on five cohorts totaling 632 Dutch twins with structural magnetic resonance imaging (MRI) data.

Actigraphic sleep and cortisol in middle childhood: A multivariate behavioral genetics model.

To date, behavioral genetic studies investigated either sleep or cortisol levels in middle childhood, but not both simultaneously. Therefore, a pertinent question is the degree to which genetic factors and environmental factor contribute to the correlation between sleep and cortisol levels. To address this question, we employed the classical twin design.

Genetic and environmental contributions to stability and change in social inhibition across the adolescent and adult life span.

Feeling inhibited and socially not at ease is reflected in the trait social inhibition (SI). SI is associated with psychopathology that arises in young adulthood, such as anxiety. We aim for a better insight into the genetic and environmental contributions to SI across the life span, and as such examine their contributions to SI stability and change across adolescent and adult life span.

DNA methylation in peripheral tissues and left-handedness.

Handedness has low heritability and epigenetic mechanisms have been proposed as an etiological mechanism. To examine this hypothesis, we performed an epigenome-wide association study of left-handedness. In a meta-analysis of 3914 adults of whole-blood DNA methylation, we observed that CpG sites located in proximity of handedness-associated genetic variants were more strongly associated with left-handedness than other CpG sites (P = 0.

Persistence of parental-reported asthma at early ages: A longitudinal twin study.

Background: Currently, we cannot predict whether a pre-school child with asthma-like symptoms will have asthma at school age. Whether genetic information can help in this prediction depends on the role of genetic factors in persistence of pre-school to school-age asthma. We examined to what extent genetic and environmental factors contribute to persistence of asthma-like symptoms at ages 3 to asthma at age 7 using a bivariate genetic model for longitudinal twin data.

Expanding the environmental scope: an environment-wide association study for mental well-being.

Background: Identifying modifiable factors associated with well-being is of increased interest for public policy guidance. Developments in record linkage make it possible to identify what contributes to well-being from a myriad of factors. To this end, we link two large-scale data resources; the Geoscience and Health Cohort Consortium, a collection of geo-data, and the Netherlands Twin Register, which holds population-based well-being data.

Incorporating Polygenic Risk Scores in the ACE Twin Model to Estimate A-C Covariance.

The assumption in the twin model that genotypic and environmental variables are uncorrelated is primarily made to ensure parameter identification, not because researchers necessarily think that these variables are uncorrelated. Although the biasing effects of such correlations are well understood, a method to estimate these parameters in the twin model would be useful. Here we explore the possibility of relaxing this assumption by adding polygenic scores to the (univariate) twin model.