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. Here we examine if polygenic measures associated with behaviors marked by low self-control interact with stressful life events in predicting self-control. Methods: Leveraging molecular data from a large population-based Dutch sample (N = 7,090, Mage = 41.2) to test for effects of genetics (i.e., polygenic scores for ADHD and aggression), stressful life events (e.g., traffic accident, violent assault, financial problems), and a gene-by-stress interaction on self-control (measured with the ASEBA Self-Control Scale). Results: Both genetics (ß =.03 -.04, p <.001) and stressful life events (ß = .11 -.14, p <.001) were associated with individual differences in self-control. We find no evidence of a gene-by-stressful life events interaction on individual differences in adults' self-control. Conclusion: Our findings are consistent with the notion that genetic influences and stressful life events exert largely independent effects on adult self-control. However, the small effect sizes of polygenic scores increases the likelihood of null results. Genetically-informed longitudinal research in large samples can further inform the etiology of individual differences in self-control from early childhood into later adulthood and its downstream implications for public health.

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). Our main aim was to test whether the associations with sex, birth weight, gestational age, and season of birth - as reported in singletons - replicate in twins, and to examine twin-specific variables, including zygosity, chorionicity, birth order, and intertwin delivery time. Compared to previously published data from adults born as singletons (7.23%), the prevalence of NRH was higher in both twins (16.19%) and their parents (15.09%). In the twins, LH and NRH were associated with parents' LH. Male sex and lower gestational age were associated with NRH, and LH was associated with not being breastfed. MH was related to neurodevelopmental delays and higher externalizing problems later in childhood. Other previously reported associations were not replicated, and no twin-specific characteristics were related to handedness. These results emphasize the importance of considering multiple definitions of handedness and indicate a small number of replicated associations across studies.

Self-rated health when population health is challenged by the COVID-19 pandemic; a longitudinal study.

RATIONALE: The coronavirus disease 2019 (COVID-19) pandemic and consequent lockdown measures have had a large impact on people's lives. Recent evidence suggests that self-rated health (SRH) scores remained relatively stable or increased during the pandemic. OBJECTIVE: For the current project, we examine potential changes in the variance decomposition of SRH before and during the COVID-19 pandemic in the Netherlands. METHODS: We analyse data from the Netherlands Twin Register to examine pre-pandemic SRH scores (N = 16,127), pandemic SRH scores (N = 17,451), and SRH difference scores (N = 7464). Additionally, we perform bivariate genetic analyses to estimate genetic and environmental variance components in pre-pandemic and pandemic SRH, and estimate the genetic correlation to assess potential gene-environment interaction. RESULTS: The majority of the sample (66.7%) reported the same SRH before and during the pandemic, while 10.8% reported a decrease, and 22.5% an increase. Individuals who reported good/excellent SRH before the pandemic were most likely to report unchanged SRH during the pandemic, and individuals with bad/mediocre/reasonable SRH more often reported increased SRH. The bivariate longitudinal genetic model reveals no significant change in variance decomposition of SRH from before to during the pandemic, with a heritability estimate of 45% (CI 36%-52%). We found that the genetic correlation could be constrained to 1, and a moderate unique environmental correlation (rE = 0.49, CI = 0.37 to 0.60). CONCLUSIONS: We theorize that the increases in SRH are explained by uninfected individuals evaluating their health more positively than under normal circumstances (partly through social comparison with infected individuals), rather than actual improvements. As the same genes are expressed under different environmental exposures, these results imply no evidence for gene-environment interaction. While different environmental factors might influence SRH at the two time-points, the influence of environmental factors does not become relatively more important during the pandemic.

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 = 0.04), but did not identify any differentially methylated positions. In longitudinal analyses of DNA methylation in peripheral blood and buccal cells from children (N = 1737), we observed moderately stable associations across age (correlation range [0.355-0.578]), but inconsistent across tissues (correlation range [- 0.384 to 0.318]). We conclude that DNA methylation in peripheral tissues captures little of the variance in handedness. Future investigations should consider other more targeted sources of tissue, such as the brain.

Genetic and environmental influences on quality of life: The COVID-19 pandemic as a natural experiment.

By treating the coronavirus disease 2019 (COVID-19) pandemic as a natural experiment, we examine the influence of substantial environmental change (i.e., lockdown measures) on individual differences in quality of life (QoL) in the Netherlands. We compare QoL scores before the pandemic (N = 25,772) to QoL scores during the pandemic (N = 17,222) in a sample of twins and their family members. On a 10-point scale, we find a significant decrease in mean QoL from 7.73 (SD = 1.06) before the pandemic to 7.02 (SD = 1.36) during the pandemic (Cohen's d = 0.49). Additionally, variance decomposition shows an increase in unique environmental variance during the pandemic (0.30-1.08), and a decrease in the heritability estimate from 30.9% to 15.5%. We hypothesize that the increased environmental variance is the result of lockdown measures not impacting everybody equally. Whether these effects persist over longer periods and how they impact health inequalities remain topics for future investigation.

Gene-by-Crisis Interaction for Optimism and Meaning in Life: The Effects of the COVID-19 Pandemic.

The corona virus disease 2019 (COVID-19) pandemic and the restrictions to reduce the spread of the virus has had a large impact on daily life. We investigated the individual differences in the effect of the COVID-19 pandemic and first lockdown on optimism and meaning in life in a sample from the Netherlands Twin Register. Participants completed surveys before (N = 9964, Mean age: 48.2, SD = 14.4) and during the first months of the pandemic (i.e. April-May 2020, N = 17,464, Mean age: 44.6 SD = 14.8), with a subsample completing both surveys (N = 6461, Mean age T1: 48.8, SD = 14.5). We applied genetic covariance structure models to twin data to investigate changes in the genetic architecture of the outcome traits due to the pandemic and the interaction of genes with the environmental exposure. Although 56% and 35% of the sample was negatively affected by the pandemic in their optimism and meaning in life, many participants were stable (32% and 43%) or even showed increased optimism and meaning in life (11% and 22%). Subgroups, specifically women, higher educated people, and people with poorer health, experienced larger negative effects. During the first months of the pandemic, slightly lower heritability estimates for optimism and meaning in life (respectively 20% and 25%) were obtained compared to pre-pandemic (respectively 26% and 32%), although confidence intervals overlap. The lower than unity genetic correlations across time (.75 and .63) suggest gene-environment interactions, where the expression of genes that influence optimism and meaning in life differs before and during the pandemic. The COVID-19 pandemic is a strong exposure that leads to imbalanced effects on the well-being of individuals. Some people decrease in well-being, while others get more optimistic and consider their lives as more meaningful during the pandemic. These differences are partly explained by individual differences in genetic sensitivity to extreme environmental change. More knowledge on the person-specific response to specific environmental variables underlying these individual differences is urgently needed to prevent further inequality.

Predicting Complex Traits and Exposures From Polygenic Scores and Blood and Buccal DNA Methylation Profiles.

We examined the performance of methylation scores (MS) and polygenic scores (PGS) for birth weight, BMI, prenatal maternal smoking exposure, and smoking status to assess the extent to which MS could predict these traits and exposures over and above the PGS in a multi-omics prediction model. MS may be seen as the epigenetic equivalent of PGS, but because of their dynamic nature and sensitivity of non-genetic exposures may add to complex trait prediction independently of PGS. MS and PGS were calculated based on genotype data and DNA-methylation data in blood samples from adults (Illumina 450 K; N = 2,431; mean age 35.6) and in buccal samples from children (Illumina EPIC; N = 1,128; mean age 9.6) from the Netherlands Twin Register. Weights to construct the scores were obtained from results of large epigenome-wide association studies (EWASs) based on whole blood or cord blood methylation data and genome-wide association studies (GWASs). In adults, MSs in blood predicted independently from PGSs, and outperformed PGSs for BMI, prenatal maternal smoking, and smoking status, but not for birth weight. The largest amount of variance explained by the multi-omics prediction model was for current vs. never smoking (54.6%) of which 54.4% was captured by the MS. The two predictors captured 16% of former vs. never smoking initiation variance (MS:15.5%, PGS: 0.5%), 17.7% of prenatal maternal smoking variance (MS:16.9%, PGS: 0.8%), 11.9% of BMI variance (MS: 6.4%, PGS 5.5%), and 1.9% of birth weight variance (MS: 0.4%, PGS: 1.5%). In children, MSs in buccal samples did not show independent predictive value. The largest amount of variance explained by the two predictors was for prenatal maternal smoking (2.6%), where the MSs contributed 1.5%. These results demonstrate that blood DNA MS in adults explain substantial variance in current smoking, large variance in former smoking, prenatal smoking, and BMI, but not in birth weight. Buccal cell DNA methylation scores have lower predictive value, which could be due to different tissues in the EWAS discovery studies and target sample, as well as to different ages. This study illustrates the value of combining polygenic scores with information from methylation data for complex traits and exposure prediction.

Genetic and Environmental Causes of Individual Differences in Borderline Personality Disorder Features and Loneliness are Partially Shared.

Loneliness is related to mental and somatic health outcomes, including borderline personality disorder. Here, we analyze the sources of variation that are responsible for the relationship between borderline personality features (including four dimensions, affective instability, identity disturbance, negative relationships, self-harm and a total score) and loneliness. Using genetically informative data from two large nonclinical samples of adult twin pairs from Australia and the Netherlands (N = 11,329), we estimate the phenotypic, genetic and environmental correlations between self-reported borderline personality features and loneliness. Individual differences in borderline personality and loneliness were best explained by additive genetic factors with heritability estimates h2 = 41% for the borderline personality total score and h2 = 36% for loneliness, with the remaining variation explained by environmental influences that were not shared by twins from the same pair. Genetic and environmental factors influencing borderline personality (total score and four subscales separately) were also partial causes of loneliness. The correlation between loneliness and the borderline personality total score was rph = .51. The genetic correlation was estimated at rg = .64 and the environmental correlation at re = .40. Our study suggests common etiological factors in loneliness and borderline personality features.

A Comparison of the ASEBA Adult Self Report (ASR) and the Brief Problem Monitor (BPM/18-59).

The adult self report (ASR) is a well-validated instrument with multiple scales relating to adult psychopathology. Recently, an 18-item version has been introduced, the brief problem monitor (BPM) to measure Internalizing behavior (INT), Externalizing behavior (EXT), and attention problems (ATT). The present study compared the BPM and ASR and investigated how well the BPM can serve as a supplement or an alternative for the ASR for specific clinical and scientific purposes. In a large sample of adult twins (N = 9.835) from the Netherlands Twin Register (NTR), we compared the internal consistency, clinical classification concordance, means, and variances of the ASR and BPM. Using the classical twin design, we investigated the genetic covariance structure. For external validation, the associations between subjective well-being and different subscales of the ASR and BPM were compared. The internal consistency of the BPM scales (around α = 0.75) was somewhat lower than the ASR (α ~ 0.85). The BPM Externalizing scale showed the lowest internal consistency (α = 0.63). ASR and BPM scores showed good clinical classification concordance (0.61-0.80) and high correlations (r > 0.88). A small reversed sex difference in the BPM Externalizing scale appeared (women > men). Genetic (0.34-0.54) and environmental components (0.46-0.66) explained the variance to a similar extent for the ASR and BPM. The phenotypic and genetic associations with well-being were comparable. In situations where sum scores are sufficient, the BPM performs as well as the longer ASR. Depending on the situation and goal, it is worth considering the BPM as an alternative for the ASR to reduce the participant burden.

Metabolomics Profile in Depression: A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls.

BACKGROUND: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons. METHODS: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses. RESULTS: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q < .05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein A1 were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms. CONCLUSIONS: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity.

The Netherlands Twin Register: Longitudinal Research Based on Twin and Twin-Family Designs.

The Netherlands Twin Register (NTR) is a national register in which twins, multiples and their parents, siblings, spouses and other family members participate. Here we describe the NTR resources that were created from more than 30 years of data collections; the development and maintenance of the newly developed database systems, and the possibilities these resources create for future research. Since the early 1980s, the NTR has enrolled around 120,000 twins and a roughly equal number of their relatives. The majority of twin families have participated in survey studies, and subsamples took part in biomaterial collection (e.g., DNA) and dedicated projects, for example, for neuropsychological, biomarker and behavioral traits. The recruitment into the NTR is all inclusive without any restrictions on enrollment. These resources - the longitudinal phenotyping, the extended pedigree structures and the multigeneration genotyping - allow for future twin-family research that will contribute to gene discovery, causality modeling, and studies of genetic and cultural inheritance.

Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine.

OBJECTIVE: To identify a plasma metabolomic biomarker signature for migraine. METHODS: Plasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a 1H-NMR-based metabolomics platform, to quantify 146 individual metabolites (e.g., lipids, fatty acids, and lipoproteins) and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with a random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Next, a global test analysis was performed to identify sets of related metabolites associated with migraine. The Holm procedure was applied to control the family-wise error rate at 5% in single-metabolite and global test analyses. RESULTS: Decreases in the level of apolipoprotein A1 (ß -0.10; 95% confidence interval [CI] -0.16, -0.05; adjusted p = 0.029) and free cholesterol to total lipid ratio present in small high-density lipoprotein subspecies (HDL) (ß -0.10; 95% CI -0.15, -0.05; adjusted p = 0.029) were associated with migraine status. In addition, only in male participants, a decreased level of omega-3 fatty acids (ß -0.24; 95% CI -0.36, -0.12; adjusted p = 0.033) was associated with migraine. Global test analysis further supported that HDL traits (but not other lipoproteins) were associated with migraine status. CONCLUSIONS: Metabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.

Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders.

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10-13) and African ancestries (rs2066702; P = 2.2 × 10-9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

Unraveling the Genetic and Environmental Relationship Between Well-Being and Depressive Symptoms Throughout the Lifespan.

Whether well-being and depressive symptoms can be considered as two sides of the same coin is widely debated. The aim of this study was to gain insight into the etiology of the association between well-being and depressive symptoms across the lifespan. In a large twin-design, including data from 43,427 twins between age 7 and 99, we estimated the association between well-being and depressive symptoms throughout the lifespan and assessed genetic and environmental contributions to the observed overlap. For both well-being (range 31-47%) and depressive symptoms (range 49-61%), genetic factors explained a substantial part of the phenotypic variance across the lifespan. Phenotypic correlations between well-being and depressive symptoms across ages ranged from -0.34 in childhood to -0.49 in adulthood. In children, genetic effects explained 49% of the phenotypic correlation while in adolescents and young adults, genetic effects explained 60-77% of the phenotypic correlations. Moderate to high genetic correlations (ranging from -0.59 to -0.66) were observed in adolescence and adulthood, while in childhood environmental correlations were substantial but genetic correlations small. Our results suggest that in childhood genetic and environmental effects are about equally important in explaining the relationship between well-being and depressive symptoms. From adolescence onwards, the role of genetic effects increases compared to environmental effects. These results provided more insights into the etiological underpinnings of well-being and depressive symptoms, possibly allowing to articulate better strategies for health promotion and resource allocation in the future.

Molecular genetic overlap between migraine and major depressive disorder.

Migraine and major depressive disorder (MDD) are common brain disorders that frequently co-occur. Despite epidemiological evidence that migraine and MDD share a genetic basis, their overlap at the molecular genetic level has not been thoroughly investigated. Using single-nucleotide polymorphism (SNP) and gene-based analysis of genome-wide association study (GWAS) genotype data, we found significant genetic overlap across the two disorders. LD Score regression revealed a significant SNP-based heritability for both migraine (h2 = 12%) and MDD (h2 = 19%), and a significant cross-disorder genetic correlation (rG = 0.25; P = 0.04). Meta-analysis of results for 8,045,569 SNPs from a migraine GWAS (comprising 30,465 migraine cases and 143,147 control samples) and the top 10,000 SNPs from a MDD GWAS (comprising 75,607 MDD cases and 231,747 healthy controls), implicated three SNPs (rs146377178, rs672931, and rs11858956) with novel genome-wide significant association (PSNP ≤ 5 × 10-8) to migraine and MDD. Moreover, gene-based association analyses revealed significant enrichment of genes nominally associated (Pgene-based ≤ 0.05) with both migraine and MDD (Pbinomial-test = 0.001). Combining results across migraine and MDD, two genes, ANKDD1B and KCNK5, produced Fisher's combined gene-based P values that surpassed the genome-wide significance threshold (PFisher's-combined ≤ 3.6 × 10-6). Pathway analysis of genes with PFisher's-combined ≤ 1 × 10-3 suggested several pathways, foremost neural-related pathways of signalling and ion channel regulation, to be involved in migraine and MDD aetiology. In conclusion, our study provides strong molecular genetic support for shared genetically determined biological mechanisms underlying migraine and MDD.

DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis.

Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry-specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95% confidence interval, 0.001-0.007; P = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 × 10-5) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the 3 fibrinogen subunit-encoding genes (FGA, FGG, and FGB) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.

Are Migraine and Tension-Type Headache Genetically Related? An Investigation of Twin Family Data.

Migraine and tension-type headache (TTH) are often viewed as distinct entities and defined as such in the International Classification of Headache Disorders, 2nd edition (ICHD-II) criteria, although there is also empirical evidence to suggest they may be etiologically similar. This study aims to investigate whether migraine and TTH are etiologically related conditions. First, we explored whether migraine and TTH were associated with the same environmental and lifestyle risk factors at the population level. Second, we examined comorbidity of migraine and TTH in a twin design. By comparing the associations in monozygotic (MZ) and dizygotic (DZ) twin pairs, we investigated whether the comorbidity can be explained by genetic factors that influence both conditions. Results indicated that migraine and TTH were largely associated with the same environmental and lifestyle factors, including younger age, female sex, higher body mass index, more depression, stress at home, and less participation in regular exercise, with consistently stronger effects for migraine than for TTH. Migraine in one twin was significantly associated with TTH in the other twin. A stronger cross-trait, cross-twin association in MZ than DZ twins suggested that this comorbidity may also be partly due to shared genetic factors, although the difference in associations was not significant. In conclusion, our findings are consistent with the hypothesis that migraine and TTH have partly shared etiologies. For both treatment and research, it may be advisable not to make a rigid distinction, but to treat migraine and TTH as related conditions.

Shared Genetics of Temporomandibular Disorder Pain and Neck Pain: Results of a Twin Study.

AIMS: (1) To examine the heritability of TMD pain and of neck pain; and (2) to estimate the potential overlap in genetic and environmental factors influencing TMD pain and neck pain. METHODS: Data from 2,238 adult female twins who completed a survey on TMD pain and neck pain were analyzed. The total variance of TMD pain and neck pain was decomposed into variance attributable to additive genetic effects and nonshared environmental effects. Bivariate structural equation modeling was applied to estimate trait-specific and genetic effects shared between traits. RESULTS: The prevalence of TMD pain and neck pain was 8.6% and 46.8%, respectively, while 6.7% of the twins reported both TMD pain and neck pain. The phenotypic correlation between TMD pain and neck pain, based on a liability threshold model, was 0.43 (95% confidence interval [CI] 0.34 to 0.51). The heritability for TMD was 0.35 (0.17 to 0.51), and for neck pain was 0.33 (0.23 to 0.43). The genetic correlation between TMD pain and neck pain was 0.64 (0.35 to 1.00), and the environmental correlation was 0.32 (0.14 to 0.48). CONCLUSION: This study shows that variation in TMD pain and neck pain can in part be attributed to genes. The comorbidity between them is partly explained by genes that influence both traits and partly by the same environmental factors.

An Extended Twin-Pedigree Study of Neuroticism in the Netherlands Twin Register.

For the participants in the Netherlands Twin Register (NTR) we constructed the extended pedigrees which specify all relations among nuclear and larger twin families in the register. A total of 253,015 subjects from 58,645 families were linked to each other, to the degree that we had information on the relations among participants. We describe the algorithm that was applied to construct the pedigrees. For > 30,000 adolescent and adult NTR participants data were available on harmonized neuroticism scores. We analyzed these data in the Mendel software package (Lange et al., Bioinformatics 29(12):1568-1570, 2013) to estimate the contributions of additive and non-additive genetic factors. In contrast to much of the earlier work based on twin data rather than on extended pedigrees, we could also estimate the contribution of shared household effects in the presence of non-additive genetic factors. The estimated broad-sense heritability of neuroticism was 47%, with almost equal contributions of additive and non-additive (dominance) genetic factors. A shared household effect explained 13% and unique environmental factors explained the remaining 40% of the variance in neuroticism.

Polygenic risk for alcohol consumption and its association with alcohol-related phenotypes: Do stress and life satisfaction moderate these relationships?

BACKGROUND: Genetic and environmental factors contribute about equally to alcohol-related phenotypes in adulthood. In the present study, we examined whether more stress at home or low satisfaction with life might be associated with heavier drinking or more alcohol-related problems in individuals with a high genetic susceptibility to alcohol use. METHODS: Information on polygenic scores and drinking behavior was available in 6705 adults (65% female; 18-83 years) registered with the Netherlands Twin Register. Polygenic risk scores (PRSs) were constructed for all subjects based on the summary statistics of a large genome-wide association meta-analysis on alcohol consumption (grams per day). Outcome measures were quantity of alcohol consumption and alcohol-related problems assessed with the Alcohol Use Disorders Identification Test (AUDIT). Stress at home and life satisfaction were moderating variables whose significance was tested by Generalized Estimating Equation analyses taking familial relatedness, age and sex into account. RESULTS: PRSs for alcohol were significantly associated with quantity of alcohol consumption and alcohol-related problems in the past year (R2=0.11% and 0.10% respectively). Participants who reported to have experienced more stress in the past year and lower life satisfaction, scored higher on alcohol-related problems (R2=0.27% and 0.29 respectively), but not on alcohol consumption. Stress and life satisfaction did not moderate the association between PRSs and the alcohol outcome measures. CONCLUSIONS: There were significant main effects of polygenic scores and of stress and life satisfaction on drinking behavior, but there was no support for PRS-by-stress or PRS-by-life satisfaction interactions on alcohol consumption and alcohol-related problems.