Genetic and environmental effects on weight gain from young adulthood to old age and its association with body mass index at early young adulthood: an individual-based pooled analysis of 16 twin cohorts.

Introduction: Genetic factors contribute to weight gain, but how these effects change over adulthood is still unknown. We studied the impact of genetics on BMI change from young adulthood to old age and its relationship with BMI in early young adulthood.

Data And Methods: Data from 16 longitudinal twin cohorts, including 111,370 adults (56% women) and 55,657 complete twin pairs (42% monozygotic), were pooled.

Polygenic scores for dizygotic twinning: insights into the genetic architecture of female fertility.

Purpose: Natural dizygotic twinning (DZT) results from hyper-ovulation and is an indicator of female fertility. However, some traits linked to DZ twinning are also associated with infertility. We examined the relationship between DZT and female (in)fertility using recent GWAS findings.

Enduring Mental Health in Childhood and Adolescence: Prevalence, Prediction, and Genetic Architecture.

Objective: The concept of enduring mental health (EMH) describes a long-term state in which a person does not experience mental disorders. Most people encounter mental health issues at some point; this study investigated the prevalence, predictors, and genetic architecture of EMH across childhood.

Method: EMH status was based on longitudinal data from 18,884 Dutch twins assessed at ages 3, 5, 7, 10, and 12 for behavioral and emotional problems.

Genome-wide association meta-analysis of age at onset of walking in over 70,000 infants of European ancestry.

Age at onset of walking is an important early childhood milestone which is used clinically and in public health screening. In this genome-wide association study meta-analysis of age at onset of walking (N = 70,560 European-ancestry infants), we identified 11 independent genome-wide significant loci. SNP-based heritability was 24.

Intergenerational transmission of complex traits and the offspring methylome.

The genetic makeup of parents can directly or indirectly affect their offspring phenome through genetic transmission or via the environment that is influenced by parental heritable traits. Our understanding of the mechanisms by which indirect genetic effects operate is limited. Here, we hypothesize that one mechanism is via the offspring methylome.

Polygenic Scores for Dizygotic Twinning: Insights into the Genetic Architecture of Female Fertility.

Natural dizygotic twinning (DZT) results from hyper-ovulation and is considered an indicator of female fertility. DZT has low polygenicity, with only 0.20% of SNPs estimated to have a nonzero effect.

The association between metabolite concentrations and wellbeing in adults.

The biological complexity of wellbeing is studied from various perspectives, including genetics and epigenetics. However, there is a knowledge gap concerning other layers, such as metabolomics, which is dynamic and changes throughout life. This study explores the association between metabolites and wellbeing in a sample (N = 4748) drawn from the Netherlands Twin Register.

Blood-Based EWAS of Asthma Polygenic Burden in The Netherlands Twin Register.

Asthma, a chronic respiratory condition characterized by airway inflammation, affects millions of individuals worldwide. Challenges remain in asthma prediction and diagnosis from its complex etiology involving genetic and environmental factors. Here, we investigated the relationship between genome-wide DNA methylation and genetic risk for asthma quantified via polygenic scores in two cohorts from the Netherlands Twin Register; one enriched with asthmatic families measured on the Illumina EPIC array (n = 526) and a general population cohort measured on the Illumina HM450K array (n = 2680).

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.

Transcriptomic and Metabolomic Analyses in Monozygotic and Dizygotic Twins.

Monozygotic (MZ) and dizygotic (DZ) twins are studied to understand genetic and environmental influences on complex traits, however the mechanisms behind twinning are not completely understood. (Epi)genomic studies identified SNPs associated with DZ twinning and DNA methylation sites with MZ twinning. To find molecular biomarkers of twinning, we compared transcriptomics and metabolomics data from MZ and DZ twins.

Epigenetic signatures of asthma: a comprehensive study of DNA methylation and clinical markers.

Background: Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma.

Methods: The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood from 319 participants from 94 families.

Building machine learning prediction models for well-being using predictors from the exposome and genome in a population cohort.

Effective personalized well-being interventions require the ability to predict who will thrive or not, and the understanding of underlying mechanisms. Here, using longitudinal data of a large population cohort (the Netherlands Twin Register, collected 1991-2022), we aim to build machine learning prediction models for adult well-being from the exposome and genome, and identify the most predictive factors ( between 702 and 5874). The specific exposome was captured by parent and self-reports of psychosocial factors from childhood to adulthood, the genome was described by polygenic scores, and the general exposome was captured by linkage of participants' postal codes to objective, registry-based exposures.

NMR metabolomics-guided DNA methylation mortality predictors.

Background: H-NMR metabolomics and DNA methylation in blood are widely known biomarkers predicting age-related physiological decline and mortality yet exert mutually independent mortality and frailty signals.

Methods: Leveraging multi-omics data in four Dutch population studies (N = 5238, ∼40% of which male) we investigated whether the mortality signal captured by H-NMR metabolomics could guide the construction of DNA methylation-based mortality predictors.

Findings: We trained DNA methylation-based surrogates for 64 metabolomic analytes and found that analytes marking inflammation, fluid balance, or HDL/VLDL metabolism could be accurately reconstructed using DNA-methylation assays.

Epigenetic Signatures of Asthma: A Comprehensive Study of DNA Methylation and Clinical Markers.

Background: Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma. The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood samples from 319 participants.

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.

No gene by stressful life events interaction on individual differences in adults' self-control.

Background: Difficulty with self-control, or the ability to alter impulses and behavior in a goal-directed way, predicts interpersonal conflict, lower socioeconomic attainments, and more adverse health outcomes. Etiological understanding, and intervention for low self-control is, therefore, a public health goal. A prominent developmental theory proposes that individuals with high genetic propensity for low self-control that are also exposed to stressful environments may be most at-risk of low levels of self-control.

Genome-Wide Association Study of Obsessive-Compulsive Symptoms including 33,943 individuals from the general population.

While 1-2% of individuals meet the criteria for a clinical diagnosis of obsessive-compulsive disorder (OCD), many more (~13-38%) experience subclinical obsessive-compulsive symptoms (OCS) during their life. To characterize the genetic underpinnings of OCS and its genetic relationship to OCD, we conducted the largest genome-wide association study (GWAS) meta-analysis of parent- or self-reported OCS to date (N = 33,943 with complete phenotypic and genome-wide data), combining the results from seven large-scale population-based cohorts from Sweden, the Netherlands, England, and Canada (including six twin cohorts and one cohort of unrelated individuals). We found no genome-wide significant associations at the single-nucleotide polymorphism (SNP) or gene-level, but a polygenic risk score (PRS) based on the OCD GWAS previously published by the Psychiatric Genetics Consortium (PGC-OCD) was significantly associated with OCS (P = 3.

Using Polygenic Scores for Circadian Rhythms to Predict Wellbeing, Depressive Symptoms, Chronotype, and Health.

The association between circadian rhythms and diseases has been well established, while the association with mental health is less explored. Given the heritable nature of circadian rhythms, this study aimed to investigate the relationship between genes underlying circadian rhythms and mental health outcomes, as well as a possible gene-environment correlation for circadian rhythms. Polygenic scores (PGSs) represent the genetic predisposition to develop a certain trait or disease.

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.

A multi-omics data analysis workflow packaged as a FAIR Digital Object.

Background: Applying good data management and FAIR (Findable, Accessible, Interoperable, and Reusable) data principles in research projects can help disentangle knowledge discovery, study result reproducibility, and data reuse in future studies. Based on the concepts of the original FAIR principles for research data, FAIR principles for research software were recently proposed. FAIR Digital Objects enable discovery and reuse of Research Objects, including computational workflows for both humans and machines.

Direct and Indirect Genetic Effects on Aggression.

Background: Family members resemble each other in their propensity for aggression. In twin studies, approximately 50% of the variance in aggression can be explained by genetic influences. However, if there are genotype-environment correlation mechanisms, such as environmental manifestations of parental and sibling genotypes, genetic influences may partly reflect environmental influences.