Unique Environmental Components Research Articles

Comorbidity Between Inflammatory Bowel Disease and Asthma and Allergic Diseases: A Genetically Informed Study.

Little is known about shared origins between inflammatory bowel disease (IBD) and allergic diseases (asthma, allergic rhinitis, and eczema). We aimed to expand current knowledge on the etiological sources of comorbidities between these disorders using a range of genetically informed methods. Within-individual and familial co-aggregation analysis was applied to 2 873 445 individuals born in Sweden from 1987 to 2014 and their first- and second-degree relatives. Quantitative genetic modeling was applied to 38 723 twin pairs to decompose the genetic and environmental sources for comorbidity. Polygenic risk score analysis between IBD and allergic diseases was conducted in 48 186 genotyped twins, and linkage disequilibrium score regression was applied using publicly available data to explore the genetic overlap. IBD was associated with asthma (adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 1.30 to 1.40), allergic rhinitis (aOR, 1.27; 95% CI, 1.20 to 1.34), and eczema (aOR, 1.47; 95% CI, 1.38 to 1.56), with similar estimates for ulcerative colitis or Crohn's disease. The ORs for familial co-aggregation decreased with decreasing genetic relatedness. Quantitative genetic modeling revealed little evidence of common genetic factors between IBD and allergic diseases (eg, IBD and allergic rhinitis; genetic correlation ra = 0.06; 95% CI, -0.03 to 0.15) but did reveal some evidence of unique environmental factors between IBD and eczema (re = 0.16; 95% CI, 0.00 to 0.32). Molecular genetic analyses were similarly null for IBD and allergic diseases, except for a slight association between Crohn's disease polygenic risk score and eczema (OR, 1.09; 95% CI, 1.06 to 1.12). We found little evidence to support a shared origin between IBD and any allergic disease but weak evidence for shared genetic and unique environmental components for IBD and eczema.

Modulation of natural killer cell exhaustion in the lungs: the key components from lung microenvironment and lung tumor microenvironment.

Lung cancer is the leading cause of tumor-induced death worldwide and remains a primary global health concern. In homeostasis, due to its unique structure and physiological function, the lung microenvironment is in a state of immune tolerance and suppression, which is beneficial to tumor development and metastasis. The lung tumor microenvironment is a more complex system that further enhances the immunosuppressive features in the lungs. NK cells are abundantly located in the lungs and play crucial roles in lung tumor surveillance and antitumor immunity. However, the immunosuppressive microenvironment promotes significant challenges to NK cell features, leading to their hypofunction, exhaustion, and compromised antitumor activity. Thus, understanding the complex interactions among the lung microenvironment, lung tumor microenvironment, and NK cell exhaustion is critical for the development of effective cancer immunotherapeutic strategies. The present review will discuss NK cell hypofunction and exhaustion within the lung microenvironment and lung tumor microenvironment, focusing on lung tissue-specific factors, including key cytokines and unique environmental components, that modulate NK cell activation and function. Understanding the functional mechanisms of key factors would help to design strategies to reverse NK cell exhaustion and restore their antitumor function within the lung tumor microenvironment.

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. Two raters placed clearly defined (semi)landmarks on each MRI scan, from which we derived 146 measures capturing the dimensions and shape of various vocal tract structures, but also aspects of the head and face. We used Genetic Covariance Structure Modeling to estimate the additive genetic, common environmental or non-additive genetic, and unique environmental components, while controlling for various confounds and for any systematic differences between the two raters. We found high heritability, h2, for aspects of the skull and face, the mandible, the anteroposterior (horizontal) dimension of the vocal tract, and the position of the hyoid bone. These findings extend the existing literature, and open new perspectives for understanding the complex interplay between genetics, environment, and culture that shape our vocal tracts, and which may help explain cross-linguistic differences in phonetics and phonology.

Heritability of Coronary Artery Disease: Insights From a Classical Twin Study.

Background:Genetics have a strong influence on calcified atherosclerotic plaques; however, data regarding the heritability of noncalcified plaque volume are scarce. We aimed to evaluate genetic versus environmental influences on calcium (coronary artery calcification) score, noncalcified and calcified plaque volumes by coronary computed tomography angiography in adult twin pairs without known coronary artery disease.Methods:In the prospective BUDAPEST-GLOBAL (Burden of Atherosclerotic Plaques Study in Twins—Genetic Loci and the Burden of Atherosclerotic Lesions) classical twin study, we analyzed twin pairs without known coronary artery disease. All twins underwent coronary computed tomography angiography to assess coronary atherosclerotic plaque volumes. Structural equation models were used to quantify the contribution of additive genetic, common environmental, and unique environmental components to plaque volumes adjusted for age, gender, or atherosclerotic cardiovascular disease risk estimate and statin use.Results:We included 196 twins (mean age±SD, 56±9 years, 63.3% females), 120 monozygotic and 76 same-gender dizygotic pairs. Using structural equation models, noncalcified plaque volume was predominantly determined by environmental factors (common environment, 63% [95% CI, 56%–67%], unique environment, 37% [95% CI, 33%–44%]), while coronary artery calcification score and calcified plaque volumes had a relatively strong genetic heritability (additive genetic, 58% [95% CI, 50%–66%]; unique environmental, 42% [95% CI, 34%–50%] and additive genetic, 78% [95% CI, 73%–80%]; unique environmental, 22% [95% CI, 20%–27%]), respectively.Conclusions:Noncalcified plaque volume is mainly influenced by shared environmental factors, whereas coronary artery calcification score and calcified plaque volume are more determined by genetics. These findings emphasize the importance of early lifestyle interventions in preventing coronary plaque formation.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01738828.

Genetic and environmental factors on heart rate, mean arterial pressure and carotid intima-media thickness: A longitudinal twin study.

Heart rate (HR), mean arterial pressure (MAP) and carotid intima-media thickness (cIMT) are moderately heritable cardiovascular traits, but the environmental effects on the longitudinal change of their heritability have never been investigated. 368 Italian and Hungarian twins (107 monozygotic, 77 dizygotic) underwent oscillometric measurement and B-mode sonography of bilateral carotid arteries in 2009/2010 and 2014. Within- -individual/cross-study wave, cross-twin/within-study wave and cross-twin/cross-study wave correlations were estimated, and bivariate Cholesky models were fitted to decompose the total variance at each wave and covariance between study waves into additive genetic, shared and unique environmental components. For each trait, a moderate longitudinal stability was observed, with within-individual/crosswave correlations of 0.42 (95% CI: 0.33-0.51) for HR, 0.34 (95% CI: 0.24-0.43) for MAP, and 0.23 (95% CI: 0.12-0.33) for cIMT. Cross-twin/cross-wave correlations in monozygotic pairs were all significant and substantially higher than the corresponding dizygotic correlations. Genetic continuity was the main source of longitudinal stability, with across-time genetic correlations of 0.52 (95% CI: 0.29-0.71) for HR, 0.56 (95% CI: 0.31-0.81) for MAP, and 0.36 (95% CI: 0.07-0.64) for cIMT. Overlapping genetic factors explained respectively 57%, 77%, and 68% of the longitudinal covariance of the HR, MAP and cIMT traits. Genetic factors have a substantial role in the longitudinal change of HR, MAP and cIMT; however, the influence of unique environmental factors remains relevant. Further studies should better elucidate whether epigenetic mechanisms have a role in influencing the stability of the investigated traits over time.

Sleep duration and post-traumatic stress disorder symptoms: a twin study.

Long and short sleep duration are associated with greater risk of developing post-traumatic stress disorder (PTSD); however, it is unknown how genetic and environmental influences affect this relationship. Thus, we investigated the association between sleep duration and PTSD symptoms using twin models. Data were obtained from 1865 monozygotic and 758 dizygotic twin pairs enrolled in the community-based Washington State Twin Registry. PTSD symptoms were assessed using the Impact of Events Scale (IES). A classical twin model decomposed the variances of sleep duration and IES score into additive genetic, shared environmental, and unique environmental components. We used correlated factor models to examine the moderation of variance components of sleep duration and IES. Shorter and longer sleep duration were associated with higher IES scores with a quadratic association (p < 0.001). The heritability of sleep duration was 36%, and IES 31%. Variance in sleep duration attributable to shared (b1C1 = 2.91, 95% CI = 1.40 to 4.43; p < 0.001) and unique (b1E1 = 0.18, 95% CI = 0.10 to 0.27; p < 0.001) environment was moderated by IES score. Similarly, but to a lesser extent, variance in IES attributable to additive genetics (b1A2 = -0.23, 95% CI = -0.45 to 0.00; p = 0.048) was moderated by sleep duration. Greater PTSD symptom severity was associated with short and long sleep duration. Increasing PTSD symptoms increased variability in sleep duration primarily via shared environmental factors, whereas decreasing sleep duration increased variability in PTSD symptoms primarily via additive genetic factors. This suggests childhood experiences affect variability of sleep duration and genetic factors affect the variability of PTSD symptoms in trauma-exposed individuals.

A Genetic Basis of Economic Egalitarianism

Studies of political attitudes and ideologies have sought to explain their origin. They have been assumed to be a result of political values ingrained during the process of socialization until early adulthood, as well as personal political experience, party affiliation, social strata, etc. As a consequence of these environment-dominated explanations, most biology-based accounts of political preference have never been considered. However, in the light of evidence accumulated in recent years, the view that political attitudes are detached from any physical properties became unsustainable. In this paper, we investigate the origins of social justice attitudes, with special focus on economic egalitarianism and its potential genetic basis. We use Minnesota Twin Study data from 2008, collected from samples of monozygotic and dizygotic twin pairs (n = 573) in order to estimate the additive genetic, shared environmental, and unique environmental components of social justice attitudes. Our results show that the large portion of the variance in a four-item economic egalitarianism scale can be attributed to genetic factor. At the same time, shared environment, as a socializing factor, has no significant effect. The effect of environment seems to be fully reserved for unique personal experience. Our findings further problematize a long-standing view that social justice attitudes are dominantly determined by socialization.

Dominant Genetic Variation and Missing Heritability for Human Complex Traits: Insights from Twin versus Genome-wide Common SNP Models

In order to further illuminate the potential role of dominant genetic variation in the "missing heritability" debate, we investigated the additive (narrow-sense heritability, h(2)) and dominant (δ(2)) genetic variance for 18 human complex traits. Within the same study base (10,682 Swedish twins), we calculated and compared the estimates from classic twin-based structural equation model with SNP-based genomic-relatedness-matrix restricted maximum likelihood [GREML(d)] method. Contributions of δ(2) were evident for 14 traits in twin models (average δ(2)twin = 0.25, range 0.14-0.49), two of which also displayed significant δ(2) in the GREMLd analyses (triglycerides δ(2)SNP = 0.28 and waist circumference δ(2)SNP = 0.19). On average, the proportion of h(2)SNP/h(2)twin was 70% for ADE-fitted traits (for which the best-fitting model included additive and dominant genetic and unique environmental components) and 31% for AE-fitted traits (for which the best-fitting model included additive genetic and unique environmental components). Independent evidence for contribution from shared environment, also in ADE-fitted traits, was obtained from self-reported within-pair contact frequency and age at separation. We conclude that despite the fact that additive genetics appear to constitute the bulk of genetic influences for most complex traits, dominant genetic variation might often be masked by shared environment in twin and family studies and might therefore have a more prominent role than what family-based estimates often suggest. The risk of erroneously attributing all inherited genetic influences (additive and dominant) to the h(2) in too-small twin studies might also lead to exaggerated "missing heritability" (the proportion of h(2) that remains unexplained by SNPs).

Twin studies in multiple sclerosis: A meta-estimation of heritability and environmentality

Background: Most twin studies of multiple sclerosis (MS) are inconclusive regarding the impact of genes and environment on disease susceptibility. In particular, high uncertainty exists about whether shared environmental factors are aetiologically relevant. Objective: To disentangle, with a reasonable degree of confidence, the relative contributions of heritability and of shared and unique environmental components of MS susceptibility. Methods: We performed a meta-analysis of previous twin studies. After a MEDLINE search, we selected eight twin studies in France, UK, Canada, Denmark, North America, Italy, Finland and Sweden. We conducted a biometric multi-group analysis under the liability-threshold model, by taking account of the study-specific ascertainment strategies and the population-specific prevalence rates of MS. Results: The meta-analytic estimates of tetrachoric correlations were 0.71 (95% confidence interval (CI): 0.67–0.74) in monozygotic pairs and 0.46 (95% CI: 0.41–0.50) in dizygotic pairs. The biometric multi-group model provided meta-analytic estimates of 0.50 (95% CI: 0.39–0.61) for heritability, 0.21 (95% CI: 0.11–0.30) for shared environmental component and 0.29 (95% CI: 0.26–0.33) for unique environmental component. Conclusion: Our results support the continuing efforts to identify unknown genetic factors that fill the gap of ‘missing heritability’; moreover, a ‘missing environmentality’ deserves future investigations into the role of non-heritable components that act as both shared and individual-specific exposures.

Do Political Attitudes and Religiosity Share a Genetic Path?

Social scientists have long recognized and sought to explain a connection between religious and political beliefs. Our research challenges the prevalent view that religion and politics constitute separate but related belief sets with a conceptual model that suggests the correlation between the two may be partially explained by an underlying psychological construct reflecting first principle beliefs on social organization. Moreover, we also push this challenge further by considering whether part of the relationship between political and religious beliefs is the result of shared genetic influences, which would suggest that a shared biological predisposition, or set of biological predispositions, underlies these attitudes. Using a classic twin design on a sample of American adults, we demonstrate that certain religious, political, and first principle beliefs can be explained by genetic and unique environmental components, and that the correlation between these three trait structures is primarily due to a common genetic path. As predicted, this relationship is found to hold for social ideology, but not for economic ideology. These findings provide evidence that the overlap between the religious and the political in the American context may in part be due to underlying principles regarding how to understand and organize society and that these principles may be adopted to satisfy biologically-influenced psychological needs.

Glycosylation of Immunoglobulin G: Role of Genetic and Epigenetic Influences

ObjectiveTo determine the extent to which genetic and epigenetic factors contribute to variations in glycosylation of immunoglobulin G (IgG) in humans.Methods76 N-glycan traits in circulating IgG were analyzed by UPLC in 220 monozygotic and 310 dizygotic twin pairs from TwinsUK. A classical twin study design was used to derive the additive genetic, common and unique environmental components defining the variance in these traits. Epigenome-wide association analysis was performed using the Illumina 27k chip. Results51 of the 76 glycan traits studied have an additive genetic component (heritability, h 2)≥ 0.5. In contrast, 12 glycan traits had a low genetic contribution (h2<0.35). We then tested for association between methylation levels and glycan levels (P<2 x10-6). Among glycan traits with low heritability probe cg08392591 maps to a CpG island 5’ from the ANKRD11 gene, a p53 activator on chromosome 16. Probe cg26991199 maps to the SRSF10 gene involved in regulation of RNA splicing and particularly in regulation of splicing of mRNA precursors upon heat shock. Among those with high heritability we found cg13782134 (mapping to the NRN1L gene) and cg16029957 mapping near the QPCT gene to be array-wide significant. The proportion of array-wide epigenetic associations was significantly larger (P<0.005) among glycans with low heritability (42%) than in those with high heritability (6.2%).ConclusionsGlycome analyses might provide a useful integration of genetic and non-genetic factors to further our understanding of the role of glycosylation in both normal physiology and disease.

Generalized anxiety disorder and anorexia nervosa: evidence of shared genetic variation

Previous studies have indicated a high prevalence of generalized anxiety disorder (GAD) in women with anorexia nervosa (AN). However, the shared genetic and environmental components of these disorders have not been explored. This study seeks to elucidate the shared genetic and environmental components between GAD and AN. Using 2,083 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, structural equation modeling was used to obtain maximum likelihood estimates of the environmental genetic, shared and unique environmental components in 496 women with GAD, 47 women with AN, 43 women with GAD + AN, and 1,497 women without GAD or AN. Results show that the heritability of GAD was 0.32 and AN was 0.31, and the genetic correlation between the two disorders was 0.20, indicating a modest genetic contribution to their comorbidity. Unique environment estimate was 0.68 for GAD and 0.69 for AN, with a unique environmental correlation of 0.18. All common environmental parameters were estimated at zero. The modest shared genetic and unique environmental liability to both disorders may help explain the high prevalence of GAD in women with AN. This knowledge could help in the treatment and prevention of comorbid disorders.

Heritability of baseline and induced micronucleus frequencies

The scoring of micronuclei (MN) is widely used in biomonitoring and mutagenicity testing as a surrogate marker of chromosomal damage inflicted by clastogenic agents or by aneugens. Individual differences in the response to a mutagenic challenge are known from studies on cancer patients and carriers of mutations in DNA repair genes. However, it has not been studied to which extent genetic factors contribute to the observed variability of individual MN frequencies. Our aim was to quantify this heritable genetic component of both baseline and radiation-induced MN frequencies. We performed a twin study comprising 39 monozygotic (MZ) and 10 dizygotic (DZ) twin pairs. Due to the small number of DZ pairs, we had to recruit controls from which 38 age- and gender-matched random control pairs (CPs) were generated. For heritability estimates, we used biometrical modelling of additive genetic, common environmental, and unique environmental components (ACE model) of variance and direct comparison of variance between the sample groups. While heritability estimates from MZ to DZ comparisons produced inconclusive results, both estimation methods revealed a high degree of heritability (h(2)) for baseline MN frequency (h(2) = 0.68 and h(2) = 0.72) as well as for the induced frequency (h(2) = 0.68 and h(2) = 0.57) when MZ were compared to CP. The result was supported by the different intraclass correlation coefficients of MZ, DZ and CP for baseline (r = 0.63, r = 0.31 and r = 0.0, respectively) as well as for induced MN frequencies (r = 0.79, r = 0.74 and r = 0.0, respectively). This study clearly demonstrates that MN frequencies are determined by genetic factors to a major part. The strong reflection of the genetic background supports the idea that MN frequencies represent an intermediate phenotype between molecular DNA repair mechanisms and the cancer phenotype and affirms the approaches that are made to utilise them as predictors of, for example, cancer risk.

A Twin Study of Depression and Migraine: Evidence for a Shared Genetic Vulnerability

To determine if shared genetic or environmental vulnerabilities could underlie depression and migraine. Depression and migraine headaches frequently coexist and their comorbidity may be due to shared etiologies. Female twins in the University of Washington Twin Registry responded to a mailed survey regarding their health history. Depression and migraine were determined by self-report of a physician's diagnosis. We used bivariate structural equation modeling to test for shared genetic, common environmental, and unique environmental components, and to estimate the magnitude of any shared component. Among 758 monozygotic and 306 dizygotic female pairs, 23% reported depression and 20% reported migraine headaches. Heritability was estimated to be 58% (95% confidence interval: 48-67%) for depression and 44% (95% confidence interval: 32-56%) for migraine. Bivariate structural equation modeling estimated that 20% of the variability in depression and migraine headaches was due to shared genes and 4% was due to shared unique environmental factors. The comorbidity of depression and migraine headache may be due in part to shared genetic risk factors. Research should focus attention on shared pathways, thereby making progress on 2 disease fronts simultaneously and perhaps providing clinicians with unified treatment strategies.

Educational attainment, smoking initiation and lifetime nicotine dependence among male Vietnam-era twins

Smoking initiation and persistence are clearly associated with factors commonly thought to be environmental in origin, including socio-economic status. However, twin models that incorporate gene-environment correlation and gene x environment interaction have not been applied to elucidate the genetic or environmental role that socio-economic status plays in smoking initiation and nicotine dependence. Twin structural equation modelling was used to examine gene-environment correlation and gene x environment interaction of one index of socio-economic status, educational attainment, with smoking initiation and nicotine dependence among 5119 monozygotic and 4295 dizygotic male-male Vietnam-era twins from the Vietnam Era Twin Registry, a national registry of twin pairs who served in the military during the Vietnam era. Educational attainment correlated significantly with smoking initiation (r=-0.27, p<0.001). Additive genetic (p=0.011), shared environment (p=0.002) and unique environment (p=0.027) components contributed to the correlation between educational attainment and smoking initiation. Educational attainment also significantly moderated the variance in smoking initiation (p<0.001), suggestive of gene x environment interaction, although the interaction with the additive genetic, shared environmental and unique environmental components could not be resolved due to multi-collinearity. In contrast, educational attainment neither correlated with nor moderated nicotine dependence, once smokers had initiated. Our study suggests that educational attainment is associated with smoking initiation, in part due to gene-environment correlation and gene x environment interaction. However, once smoking initiation is taken into account, there are no effects--be they gene-environment correlation or gene x environmental interaction--of educational attainment on nicotine dependence.