Unique Environmental Contributions Research Articles

Heritability of the glycan clock of biological age.

Immunoglobulin G is posttranslationally modified by the addition of complex N-glycans affecting its function and mediating inflammation at multiple levels. IgG glycome composition changes with age and health in a predictive pattern, presumably due to inflammaging. As a result, a novel biological aging biomarker, glycan clock of age, was developed. Glycan clock of age is the first of biological aging clocks for which multiple studies showed a possibility of clock reversal even with simple lifestyle interventions. However, none of the previous studies determined to which extent the glycan clock can be turned, and how much is fixed by genetic predisposition. To determine the contribution of genetic and environmental factors to phenotypic variation of the glycan clock, we performed heritability analysis on two TwinsUK female cohorts. IgG glycans from monozygotic and dizygotic twin pairs were analyzed by UHPLC and glycan age was calculated using the glycan clock. In order to determine additive genetic, shared, and unique environmental contributions, a classical twin design was applied. Heritability of the glycan clock was calculated for participants of one cross-sectional and one longitudinal cohort with three time points to assess the reliability of measurements. Heritability estimate for the glycan clock was 39% on average, suggesting a moderate contribution of additive genetic factors (A) to glycan clock variation. Remarkably, heritability estimates remained approximately the same in all time points of the longitudinal study, even though IgG glycome composition changed substantially. Most environmental contributions came from shared environmental factors (C), with unique environmental factors (E) having a minor role. Interestingly, heritability estimates nearly doubled, to an average of 71%, when we included age as a covariant. This intervention also inflated the estimates of unique environmental factors contributing to glycan clock variation. A complex interplay between genetic and environmental factors defines alternative IgG glycosylation during aging and, consequently, dictates the glycan clock's ticking. Apparently, environmental factors (including lifestyle choices) have a strong impact on the biological age measured with the glycan clock, which additionally clarifies why this aging clock is one of the most potent biomarkers of biological aging.

BEHAVIORAL GENETICS FOUNDATIONS OF RELATIONS BETWEEN PERSONALITY TRAITS AND SATISFACTION WITH LIFE

The long-term stability of subjective wellbeing has directed an attention to stable dispositions as the probable source of individual differences in the satisfaction with life (SWL). The main objective of this study was to examine the extent of genetic overlap between SWL and personality traits of the five-factor model (FFM). The sample consisted of 121 monozygotic and 61 dizygotic twin pairs (the average age was 24.59, SD = 7.11). Satisfaction with Life Scale and The Revised NEO Personality Inventory (NEO-PIR) were applied. Multivariate genetic modeling was performed. The results show the most appropriate fit indices for Independent AE model(χ²/df = 1.41, CFI = .92, TLI = .91, RMSEA = .07, AIC = 17400.81, BIC = 17558.68, SRMR = .10). SWL and all NEOPI- R personality traits have a moderate to strong genetic bases, while the common genetic influences for SWL are 40%. The results show that unique environmental contributions are moderate to strong (from 61% for Neuroticism, 41% for SWL, to 23% for Conscientiousness). Genetically driven tendency common to Neuroticism, Extraversion, and Conscientiousness, underlines individual differences in SWL, and therefore a cognitive evaluation of SWL seems to be substantially based on emotional tendencies encompassed by the FFM. Also, SWL appears to be uniquely environmentally influenced, which implies benefits of wellbeing interventions through the process of learning or adopting a different life philosophy.

Subacromial Space Width: Does Overuse or Genetics Play a Greater Role in Determining It? An MRI Study on Elderly Twins.

Age and peripheral microcirculation disorders are the main causes of rotator cuff degeneration. Acromion variants may affect subacromial space width, causing a pathological narrowing of the space that may compromise the cuff integrity. However, it is not clear if the subacromial space width is genetically determined or if it changes according to loading conditions. To clarify this unresolved question, we performed an MRI (magnetic resonance imaging) study with the aim of evaluating the acromiohumeral distance in a group of elderly monozygotic and dizygotic twins, and we analyzed the obtained data using the twin design to separate the contributions of shared and unique environments. We identified twenty-nine pairs of elderly twins. On MRI scans, we evaluated the acromiohumeral distance and health status of the rotator cuff tendons. Heritability, defined as the proportion of total variance of a specific characteristic in a particular population due to a genetic cause, was estimated as twice the difference between the intraclass correlation coefficients for monozygotic and dizygotic pairs. The influence of shared environment, due to environmental factors that contribute to twin and sibling similarity, was calculated as the difference between the monozygotic correlation coefficient and the heritability index. One-way ANOVA (analysis of variance) was used to estimate the differences among job categories, both in the total cohort and within zygosity groups. The intraclass correlation coefficient was substantially higher for monozygotic than for dizygotic twins, indicating a high degree of concordance of the acromiohumeral distance in pairs of individuals who shared 100% of their genes. The heritability index was 0.82, and shared and unique environmental contributions were both 0.09. There were no significant differences among subjects in different job categories, either in the total cohort (p = 0.685) or within the monozygotic (p = 0.719) and dizygotic groups (p = 0.957). The acromiohumeral distance is mainly genetically determined and only marginally influenced by external factors.

The Genetic and Environmental Determinants of the Association Between Brain Abnormalities and Schizophrenia: The Schizophrenia Twins and Relatives Consortium

BackgroundStructural brain abnormalities are consistently found in schizophrenia (Sz) and have been associated with the familial risk for the disorder. We aim to define the relative contributions of genetic and nongenetic factors to the association between structural brain abnormalities and Sz in a uniquely powered cohort (Schizophrenia Twins and Relatives consortium).MethodsAn international multicenter magnetic resonance imaging collaboration was set up to pool magnetic resonance imaging scans from twin pairs in Utrecht (The Netherlands), Helsinki (Finland), London (United Kingdom), and Jena (Germany). A sample of 684 subjects took part, consisting of monozygotic twins (n = 410, with 51 patients from concordant and 52 from discordant pairs) and dizygotic twins (n = 274, with 39 patients from discordant pairs). The additive genetic, common, and unique environmental contributions to the association between brain volumes and risk for Sz were estimated by structural equation modeling.ResultsThe heritabilities of most brain volumes were significant and ranged between 52% (temporal cortical gray matter) and 76% (cerebrum). Heritability of cerebral gray matter did not reach significance (34%). Significant phenotypic correlations were found between Sz and reduced volumes of the cerebrum (−.22 [−.30/−.14]) and white matter (−.17 [−.25/−.09]) and increased volume of the third ventricle (.18 [.08/.28]). These were predominantly due to overlapping genetic effects (77%, 94%, and 83%, respectively).ConclusionsSome of the genes that transmit the risk for Sz also influence cerebral (white matter) volume.

Investigating Unique Environmental Contributions to the Neural Representation of Written Words: A Monozygotic Twin Study

The visual word form area (VWFA) is a region of left inferior occipitotemporal cortex that is critically involved in visual word recognition. Previous studies have investigated whether and how experience shapes the functional characteristics of VWFA by comparing neural response magnitude in response to words and nonwords. Conflicting results have been obtained, however, perhaps because response magnitude can be influenced by other factors such as attention. In this study, we measured neural activity in monozygotic twins, using functional magnetic resonance imaging. This allowed us to quantify differences in unique environmental contributions to neural activation evoked by words, pseudowords, consonant strings, and false fonts in the VWFA and striate cortex. The results demonstrate significantly greater effects of unique environment in the word and pseudoword conditions compared to the consonant string and false font conditions both in VWFA and in left striate cortex. These findings provide direct evidence for environmental contributions to the neural architecture for reading, and suggest that learning phonology and/or orthographic patterns plays the biggest role in shaping that architecture.

Genetic and environmental contributions to self‐reported thoughts of self‐harm and suicide

Thoughts of self-harm and suicidal behavior are thought to be influenced by both genetics and environment. Molecular genetic studies are beginning to address the question of which genes may be involved and whether different genes may be expressed in men and women. We examined thoughts of self-harm and suicidal behavior in a large general population twin sample including male and female same- and opposite-sex twins. In this study, data on self-reported thoughts of self-harm and suicide were obtained from self-report questionnaires (Beck Depression Inventory and Youth or Adult Self Report forms) in 6,265 twin pairs (11,008 individuals) aged 11-90 (62% female) from the Netherlands Twin Registry. Liability threshold models were compared including sex and age (linear and quadratic) effects. Models were compared using measures of parsimony to calculate the simplest model to the data. A model with additive genetic and unique environmental contributions fitted the data for both males and females. There were no qualitative sex differences, but the relative contributions differed between men and women. Heritability was higher in women (0.74, 95% CI 0.65-0.81) than men (0.45, 95% CI 0.28-0.61). The remaining variance was accounted for by environmental influence unique to an individual. These results suggest contributions from additive genetic factors to self-reported thoughts of self-harm and suicide and support the continued study of both molecular genetic and individual-specific environmental risk factors.

Shared genetic contributions to anxiety disorders and pathological gambling in a male population

Pathological gambling (PG) frequently co-occurs with anxiety disorders. However, the extent to which the co-occurrence is related to genetic or environmental factors across PG and anxiety disorders is not known. Data from the Vietnam Era Twin Registry (n=7869, male twins) were examined in bivariate models to estimate genetic and shared and unique environmental contributions to PG and generalized anxiety disorder (GAD) and PG and panic disorder (PD). While both genetic and unique environmental factors contributed individually to PG, GAD, and PD, the best fitting model indicated that the relationship between PG and GAD was attributable predominantly to shared genetic contributions (r(A)=0.53). In contrast, substantial correlations were observed between both the genetic (r(A)=0.34) and unique environmental (r(E)=0.31) contributions to PG and PD. Results may be limited to middle aged males. The existence of shared genetic contributions between PG and both GAD and PD suggests that specific genes, perhaps those involved in affect regulation or stress responsiveness, contribute to PG and anxiety disorders. Overlapping environmental contributions to the co-occurrence of PG and PD suggest that common life experiences (e.g., early life trauma) contribute to both PG and PD. Conversely, the data suggest that distinct environmental factors contribute to PG and GAD (e.g., early onset of gambling in PG). Future studies should examine the relationship between PG and anxiety disorders amongst other populations (women and adolescents) to identify specific genetic and environmental influences that account for the manifestation of these disorders and their co-occurrences.

Posttraumatic stress disorder; combat exposure; and nicotine dependence, alcohol dependence, and major depression in male twins

Combat exposure is associated with increased risk of psychiatric and substance use disorders in veterans. However, it is not known whether combat exposure independently increases risk for these disorders or whether this association is accounted for by genetic vulnerability common to posttraumatic stress disorder (PTSD). This article tests competing explanations for the association of combat exposure and PTSD with nicotine dependence (ND), alcohol dependence (AD), and major depression (MD). Data were obtained from 6099 members of the Vietnam Era Twin Registry, a national registry of male-male twin pairs who served in the military during the Vietnam era. Twin models were fit to estimate the genetic and environmental variance common and specific to Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, lifetime diagnoses of PTSD, combat trauma, and 3 comorbid conditions: ND, AD, and MD. Variance specific to ND, AD, and MD was due to genetic factors (48%, 36%, and 12%, respectively) and unique environmental factors (36%, 42%, and 58%, respectively). After accounting for variance common to PTSD, no residual genetic and environmental variance overlapped between combat and ND, combat and AD, and combat and MD. Combat exposure is not independently associated with lifetime ND, AD, and MD. The association of combat exposure with these 3 disorders is due to genetic and unique environmental contributions in common with PTSD. These findings suggest comorbid PTSD may represent a genetically mediated vulnerability to psychopathology after trauma.

Genetic analysis of physical activity in twins

The reduced contribution of physical activity (PA) to daily energy expenditure contributes to the increased prevalence of obesity. A genetic control of activity-induced energy expenditure (AEE) may contribute to a genetic susceptibility to obesity. Our aim was to investigate the relative contribution of genetic and environmental factors to the variation and covariation in AEE and PA. Twelve monozygotic and 8 same-sex dizygotic (including 2 same-sex sibling pairs; age differences: 2 and 2.5 y) twin pairs aged between 18 and 39 y participated. AEE was measured in a respiration chamber for 24 h and with doubly labeled water in daily life for 2 wk. PA was recorded simultaneously with a triaxial accelerometer. Structural equation modeling was used to separate and quantify the observed variance into sex-adjusted additive genetic and common and unique environmental contributions. In the respiration chamber, common and unique environmental factors explained the variance in AEE and PA, and no genetic contribution was found. In daily life, genetic factors explained 72% of the variance in AEE and 78% of the variance in PA. Unique environmental factors explained the remaining variance. The same additive genetic factors explained 67% of the covariance in AEE and PA in daily life. In the present exploratory study that used gold standard measurements for AEE and PA but a limited sample size, genetic influence explained a large part of the variation in AEE and PA in daily life, whereas both AEE and PA were influenced by environment only within the confined area of the respiration chamber.

Analysis of Melanoma Onset: Assessing Familial Aggregation by Using Estimating Equations and Fitting Variance Components via Bayesian Random Effects Models

We investigate whether relative contributions of genetic and shared environmental factors are associated with an increased risk in melanoma. Data from the Queensland Familial Melanoma Project comprising 15,907 subjects arising from 1912 families were analyzed to estimate the additive genetic, common and unique environmental contributions to variation in the age at onset of melanoma. Two complementary approaches for analyzing correlated time-to-onset family data were considered: the generalized estimating equations (GEE) method in which one can estimate relationship-specific dependence simultaneously with regression coefficients that describe the average population response to changing covariates; and a subject-specific Bayesian mixed model in which heterogeneity in regression parameters is explicitly modeled and the different components of variation may be estimated directly. The proportional hazards and Weibull models were utilized, as both produce natural frameworks for estimating relative risks while adjusting for simultaneous effects of other covariates. A simple Markov Chain Monte Carlo method for covariate imputation of missing data was used and the actual implementation of the Bayesian model was based on Gibbs sampling using the free ware package BUGS. In addition, we also used a Bayesian model to investigate the relative contribution of genetic and environmental effects on the expression of naevi and freckles, which are known risk factors for melanoma.

Analysis of melanoma onset: assessing familial aggregation by using estimating equations and fitting variance components via Bayesian random effects models.

We investigate whether relative contributions of genetic and shared environmental factors are associated with an increased risk in melanoma. Data from the Queensland Familial Melanoma Project comprising 15,907 subjects arising from 1912 families were analyzed to estimate the additive genetic, common and unique environmental contributions to variation in the age at onset of melanoma. Two complementary approaches for analyzing correlated time-to-onset family data were considered: the generalized estimating equations (GEE) method in which one can estimate relationship-specific dependence simultaneously with regression coefficients that describe the average population response to changing covariates; and a subject-specific Bayesian mixed model in which heterogeneity in regression parameters is explicitly modeled and the different components of variation may be estimated directly. The proportional hazards and Weibull models were utilized, as both produce natural frameworks for estimating relative risks while adjusting for simultaneous effects of other covariates. A simple Markov Chain Monte Carlo method for covariate imputation of missing data was used and the actual implementation of the Bayesian model was based on Gibbs sampling using the free ware package BUGS. In addition, we also used a Bayesian model to investigate the relative contribution of genetic and environmental effects on the expression of naevi and freckles, which are known risk factors for melanoma.

A twin study of generalized anxiety disorder symptoms, panic disorder symptoms and post-traumatic stress disorder in men

Generalized anxiety disorder (GAD), panic disorder (PD) and post-traumatic stress disorder (PTSD) often co-occur. We investigated whether and to what degree genetic and environmental contributions overlap among symptoms of GAD, symptoms of PD and PTSD. Subjects were 3327 monozygotic and dizygotic male–male twin pair members of the Vietnam Era Twin Registry who participated in a 1992 telephone administration of the Diagnostic Interview Schedule Version 3 Revised (DIS3R). Genetic model fitting was performed to estimate the magnitude of genetic and environmental contributions to the lifetime co-occurrence of GAD symptoms, PD symptoms and PTSD. The liability for GAD symptoms was due to a 37.9% additive genetic contribution common to PD symptoms and PTSD. Liability for PD symptoms was due to a 20.7% additive genetic contribution common to GAD symptoms and PTSD, and a 20.1% additive genetic influence specific to PD symptoms. Additive genetic influences common to symptoms of GAD and PD accounted for 21.3% of the genetic variance in PTSD. Additive genetic influences specific to PTSD accounted for 13.6% of the genetic variance in PTSD. Remaining variance for all three disorders was due to unique environmental factors both common and specific to each phenotype. These results suggest that these disorders each have etiologically distinct components and also have significant genetic and unique environmental contributions in common.

Genetic and environmental influences on posttraumatic stress disorder, alcohol and drug dependence in twin pairs

We investigated whether and to what degree genetic and environmental contributions overlap among posttraumatic stress disorder (PTSD), alcohol dependence (AD) and drug dependence (DD). Subjects were 3304 monozygotic and dizygotic male–male twin pair members of the Vietnam Era Twin Registry who participated in 1992 telephone administration of the Diagnostic Interview Schedule Version 3 Revised (DIS-3R). Genetic model fitting was performed to estimate the magnitude of genetic and environmental contributions to the lifetime co-occurrence of DSM-III-R PTSD, AD and DD. The liability for PTSD was partially due to a 15.3% genetic contribution common to AD and DD and 20.0% genetic contribution specific to PTSD. Risk for AD was partially due to a 55.7% genetic contribution common to PTSD and DD. Genetic influences common to PTSD and AD accounted for 25.2% of the total risk for DD. Specific family environmental influence accounted for 33.9% of the total variance in risk for DD. Remaining variance for all three disorders was due to unique environmental factors both common and specific to each phenotype. These results suggest that PTSD, AD and DD each have etiologically distinct components and also have significant genetic and unique environmental contributions in common.