Twin Population Research Articles

Heritability of the timing of food intake

While environmental factors are presumed to be primary drivers of food timing, preliminary evidence suggests that genetics may be an additional determinant. The aim was to explore the relative contribution of genetics and environmental factors to variation in the timing of food intake in a Spanish twin population. Because chronotype, bedtime and wake time are related to food timing, covariance with food timing was further assessed. In this observational study, 53 pairs of adult (mean (SD)=52 (6.03) years) female twins (28 monozygotic; 25 dizygotic) were recruited from the Murcia Twin Register. Zygosity was determined by DNA-testing. Timing of the three main meals of the day was assessed via 7-day dietary records, and the midpoint of food intake was computed by calculating the midpoint between breakfast and dinner times. Chronotype, bedtime and wake time were self-reported. Heritability of food timing and related traits were estimated by comparing monozygotic and dizygotic twin correlations and fitting genetic structural equation models to measured variables. We observed genetic influences for food timing, with highest heritability for the midpoint of food intake (64%) in an overweight/obese population (BMI=26.01±3.77). Genetic factors contributed to a higher degree to the timing of breakfast (56%) than the timing of lunch (38%) or dinner (n.s.). Similarly, heritability estimates were larger in related behavioral traits earlier on in the day (i.e. wake time, (55%)), than those later on in the day (i.e. bedtime, (38%)). Bivariate analyses revealed a significant genetic overlap between food timing and bedtime and chronotype (rG between 0.78 and 0.91). Genetic influences appear to account for a significant proportion of the variability in food timing, particularly breakfast. Thus, interventions related to food timing may be more effective when targeting afternoon/evening traits, such as lunch or dinner times. Furthermore, our data suggest shared genetic architecture underlying food timing and phenotypically related traits. NCT03059576. https://clinicaltrials.gov/ct2/show/NCT03059576.

Digital Twins in Health Care: Ethical Implications of an Emerging Engineering Paradigm.

Personalized medicine uses fine grained information on individual persons, to pinpoint deviations from the normal. ‘Digital Twins’ in engineering provide a conceptual framework to analyze these emerging data-driven health care practices, as well as their conceptual and ethical implications for therapy, preventative care and human enhancement. Digital Twins stand for a specific engineering paradigm, where individual physical artifacts are paired with digital models that dynamically reflects the status of those artifacts. When applied to persons, Digital Twins are an emerging technology that builds on in silico representations of an individual that dynamically reflect molecular status, physiological status and life style over time. We use Digital Twins as the hypothesis that one would be in the possession of very detailed bio-physical and lifestyle information of a person over time. This perspective redefines the concept of ‘normality’ or ‘health,’ as a set of patterns that are regular for a particular individual, against the backdrop of patterns observed in the population. This perspective also will impact what is considered therapy and what is enhancement, as can be illustrated with the cases of the ‘asymptomatic ill’ and life extension via anti-aging medicine. These changes are the consequence of how meaning is derived, in case measurement data is available. Moral distinctions namely may be based on patterns found in these data and the meanings that are grafted on these patterns. Ethical and societal implications of Digital Twins are explored. Digital Twins imply a data-driven approach to health care. This approach has the potential to deliver significant societal benefits, and can function as a social equalizer, by allowing for effective equalizing enhancement interventions. It can as well though be a driver for inequality, given the fact that a Digital Twin might not be an accessible technology for everyone, and given the fact that patterns identified across a population of Digital Twins can lead to segmentation and discrimination. This duality calls for governance as this emerging technology matures, including measures that ensure transparency of data usage and derived benefits, and data privacy.

Predictors and consequences of health anxiety symptoms: a novel twin modeling study.

The question of how to best conceptualize health anxiety (HA) from a diagnostic and etiological perspective remains debated. The aim was to examine the relationship between HA and the symptoms of anxiety and obsessive-compulsive-related disorders in a normative twin population. Four hundred and ninety-six monozygotic adult twin pairs from the Australian Twin Registry participated in the study (age, 34.4 ± 7.72 years; 59% females). Validated scales were used to assess each domain. We applied a twin regression methodology-ICE FALCON-to determine whether there was evidence consistent with 'causal' relationships between HA and other symptoms by fitting and comparing model estimates. Estimates were consistent with higher levels of obsessing ('unwanted thoughts') (P = 0.008), social anxiety (P = 0.03), and body dysmorphic symptoms (P = 0.008) causing higher levels of HA symptoms, and with higher levels of HA symptoms causing higher levels of physical/somatic anxiety symptoms (P = 0.001). Obsessional thoughts, body dysmorphic concerns, and social anxiety symptoms may have a causal influence on HA. To report physical/somatic anxiety appears to be a consequence of the underlying presence of HA-related fears. Should our results be confirmed by longitudinal studies, the evaluation and treatment of HA may benefit from the consideration of these identified risk factors.

Heritability and correlation of lip print, palm print, fingerprint pattern and blood group in twin population.

Background:Twins are similar in many ways owing to the genetical and environmental factors. However, still, there are certain things that are not similar among them, and this is the challenge for personal identification among the twins.Objectives:Our present study aimed to know and assess the similarities and differences present between the monozygotic (identical) and dizygotic (fraternal) twins in relation to lip prints, palm prints, fingerprints and blood group and to evaluate their heritability among parents and their offspring.Materials and Methods:The study group comprised 30 twins and their parents – 15 identical and 15 nonidentical twins. The age of twins ranged from 15 years to 40 years. Lip print, palm print, fingerprint and blood group were statistically analyzed.Results:All the data were subjected to statistical analysis. The identical twins showed more percentage of similarities in comparison to the non identical twins. The inheritance pattern was significant for twins in case of their lip prints while palm prints and finger prints showed no such significance in inheritance pattern whereas there was significant association seen in case of blood groups of identical twins and their parents.Conclusion:Lip prints, palm prints, fingerprints and blood groups are the important parameters in forensic science for individual identification. Many studies have been done till now in individual but very few studies done in twin population. To the best of knowledge, ours is the first study of its kind with multiple parameters and its heritability in twins. We have observed that heritability in twins with relation to lip print was statistically significant and all the parameters can be used independently to identify the twins.

Genetic influence on femoral plaque and its relationship with carotid plaque: an international twin study.

To disentangle genetic and environmental influences on the development of femoral plaques using a population of adult twins. To evaluate the potential role of shared genetic and environmental factors in the co-occurrence of femoral and carotid plaques. The sample included 566 twins belonging to 164 monozygotic (MZ) and 119 dizygotic (DZ) twin pairs, who underwent peripheral arterial assessment by B-mode ultrasound in different centers. The variance in femoral plaques onset was due to genetic factors and the remaining 50% was explained by common (15%) and unique (35%) environmental factors. Findings on sidedness and number of femoral plaques indicated that also these traits were mainly under genetic control. No effect of common environment was found on plaques composition, and variability of this trait was explained by genetics (64%) and unique environment (36%). Covariation between the liabilities to carotid and femoral plaques was mainly attributed to shared genes (77%), with the remaining 23% explained by individual-specific environmental factors shared by the two districts. Inter-individual differences in plaque onset as well as in their number, sidedness and composition are mainly genetic in origin. The results on the cooccurrence of carotid and femoral plaque underline the genetic role in atherogenesis.

Twin transvaginal cervical length at 16–20 weeks and prediction of preterm birth

Objective: Our objective was to determine if transvaginal cervical length at 16–20 weeks is predictive of preterm birth <34 weeks in a large cohort of twin pregnancies.Study design: This is a secondary analysis from a randomized trial of 17 alpha-hydroxyprogesterone caproate in twins to prevent preterm birth. Transvaginal cervical length was performed at 16–20-week gestation. The inclusion criteria were non-anomalous twins with transvaginal cervical length at 16–20 weeks. Receiver-operating characteristic (ROC) curves were generated to determine the transvaginal cervical length associated with preterm birth.Results: Of 655 pregnancies, 27% (N = 178) women met our inclusion criteria. The rate of spontaneous preterm birth before 34 weeks was 16% (N = 29). A receiver operator characteristic curve was generated for all preterm birth <34 weeks (spontaneous and indicated) which demonstrated an area under the curve of 0.51, 95% CI (0.41–0.61). When indicated preterm birth (n = 15) were excluded, the area under the curve was 0.59 (95% CI 0.47–0.70), indicating that transvaginal cervical length values were not a clinically useful test for the prediction of spontaneous preterm birth. A transvaginal cervical length of 30 mm from this model would produce a sensitivity of detecting spontaneous preterm birth of 95% and a specificity of 14%.Conclusion: In an asymptomatic twin population, a single transvaginal cervical length between 16 and 20 weeks was not predictive of spontaneous preterm birth before 34 weeks. Thus, our findings suggest that routine transvaginal cervical length screening of twins should not be performed between 16–20 weeks.

PP-26 Neocord: mrna expression of cytochromes and transporters involved in drug metabolism at birth, using human umbilical cord blood

Background Growth, maturation and physiological modifications are mainly responsible for the difference in pharmacokinetics and pharmacodynamics of drugs ob-served between adults and children, especially neonates. Ontogeny of drug metabolising enzymes and transport-ers play an important role in drugs inter-individual phar-macokinetic variability in this population. Data on neona-tal developmental pharmacology remain very limited. Neocord aims to characterise mRNA expression of the main cytochromes and transporters involved in the phar-macokinetics and pharmacodynamics of drugs in twin newborns, using umbilical cord blood, according to iden-tified covariates such as genetic background, pregnancy environment, gestational age, sex, maternal pathologies and treatments, etc. A population of twins will allow a precise comparison of individuals with different or identi-cal genetic background. Methods Umbilical cord blood samples (2.5 ml) were col-lected from women pregnant with twins, both dizygotic and monozygotic, in the maternity ward of Robert-Debre Hospital using PaxGene Blood RNA tubes. Isolation and purification of total RNA from the blood samples was performed using the PAXgene Blood RNA kit with sub-sequent RNA reverse transcription (RT-PCR). Amplification of DNA and gene expression profiling was performed by real-time polymerase chain reaction (qPCR) using Ap-plied Biosystems TaqMan gene expression assay tech-nology. Expression of the 18S ribosomal reference gene was used as internal control for normalisation of expres-sion profiles. A large panel of drug metabolising enzymes and transporters genes was quantified: cytochrome P450 system (n=12), UGT family (n=6), transporters (n=3) and TPMT. Relative gene expression levels between the differ-ent samples were calculated using the ΔΔCt method. Results Fifty umbilical cord blood samples (32 males and 18 females) from 25 women pregnant with twins, deliv-ering between April 2015 and March 2017, were collect-ed. Median age of the women was 33.2 years (23.2–49.5) and median gestational age at delivery was 37.3 weeks of amenorrhea (34.4–39.6). Nineteen women delivered at term and 6 delivered before 37 weeks. Five women had a monochorionic diamniotic pregnancy and 20 women had a dichorionic diamniotic pregnancy. Monochorionic twins were assumed to be monozygotic (n=10) and dif-ferent-sex twins as dizygotic (n=20). Zygosity of the 20 same-sex dichorionic twins could not be assessed. Preliminary results were obtained after analysis of 30 cord blood samples. Females (n=12) and males (n=18) showed no differences of weight or gestational age at birth. From these 15 twins pairs: UGT1A6 and UGT2B7 expressions were not found in umbilical cord blood samples while others were expressed at different levels. Gene expression was different between newborn genders (p Conclusion Identification of differences in protein ex-pression profiles will allow a better understanding of the pharmacokinetics and pharmacodynamics variability of drugs in the newborn. Such factors will help improving neonatal care and define appropriate dose regimens in the neonatal population.

Abstract P127: Chromogranin A Pathway: From Pathogenic Molecule to Renal Disease

Introduction: Chromogranin A (CHGA) is released into circulation with catecholamine from secretory granules of chromaffin cells and post-ganglionic sympathetic neurons. Several CHGA gene polymorphisms contributing to traits of autonomic blood pressure control, hypertension and hypertensive nephropathy have been identified. Plasma CHGA is elevated in hypertension and renal failure. This study seeks to understand the role of CHGA in the progression of CKD/ ESRD. Hypothesis: Kidney injury results in elevated expression of CHGA which in turn affects biochemical and physiological traits that determine progression and development of CKD/ESRD. Methods: The remnant kidney model was used to investigate the influence of CHGA on kidney function in response to injury. Distinction in response to kidney injury in wild-type (WT) and Chga-/- (KO) mice was evaluated by measuring glomerular function, fibrosis and microarray analysis. Mesangial cells were treated with CHGA to delineate pathway leading to inflammation and fibrosis. Results: Nephrectomy (Npx) exacerbated azotemia in WT mice compared to their KO counterparts. WT-Npx mice displayed far excess fibrosis as equated with KO-Npx. Gene expression profiling revealed greater mitochondrial dysfunction due to Npx in WT mice. Mesangial cells in culture treated with CHGA, triggered NO release, by a signaling mechanism involving SR-A. CHGA treatment augmented NO production by a 2-step mechanism involving upregulation of iNOS and the arginine transporter Slc7a7. CHGA-treated vs. untreated cells exhibited differential involvement of cytokine, chemokine, complement, acute phase pro-inflammatory markers and apoptotic pathway genes. Plasma creatinine and CHGA was measured in a twin population (N=740) and an inverse correlation between GFR and CHGA was observed. Therefore, in both mice and humans an inverse correlation suggested decrease in glomerular function with increasing plasma CHGA concentration. Conclusions: Kidney injury leads to elevated levels of CHGA which serves as an insult to the mesangial cells resulting in reduction of mitochondrial efficiency, concerted transcription of genes involved in NO production, inflammation and fibrosis, progression of CKD and development of ESRD.

Negative social comparisons and psychosis proneness in a healthy adolescent population

There is growing evidence of an association between negative social comparisons (NSC) and both psychosis, and psychosis proneness. The majority of the work thus far, however, has focused largely on one type of NSC, namely, social rank. Whilst social rank is clearly an important factor, an individual's perception of belonging is likely also of importance; particularly, when considering individuals from collectivistic cultures such as China, where greater emphasis is placed on fitting into the group. There is also limited research investigating what factors may contribute towards the relationship between NSC and psychosis proneness, and to what extent this relationship may be due to common familial factors. To address these issues, we examined whether (1) Social rank and perceived belonging predict negative, positive and depressive psychotic experiences in a Chinese, adolescent, twin and sibling population, (2) coping styles moderate the impact of these relationships and (3), there is a familial association between NSC and psychosis proneness. Both social rank and perceived belonging were found to predict the negative and depressive dimensions of psychosis. These relationships were moderated by problem-focused coping styles. Interestingly, the association between perception of belonging, and negative psychotic experiences was familial—and stronger in Monozygotic twins—indicating perhaps shared aetiology due to common genes. Our findings highlight NSC as potential vulnerability markers for negative and depressive psychotic experiences, and suggest potentially different aetiological pathways amongst different NSC and different psychotic experiences. On a clinical level, our findings emphasize the need to consider coping styles when treating at-risk individuals.

Febrile Seizures and Epilepsy: Association With Autism and Other Neurodevelopmental Disorders in the Child and Adolescent Twin Study in Sweden

BackgroundThere is a recently well-documented association between childhood epilepsy and earlysymptomaticsyndromeselicitingneurodevelopmentalclinicalexaminations (ESSENCE) including autism spectrum disorder, but the relationship between febrile seizures and ESSENCE is less clear. MethodsThe Child and Adolescent Twin Study in Sweden (CATSS) is an ongoing population-based study targeting twins born in Sweden since July 1, 1992. Parents of 27,092 twins were interviewed using a validated DSM-IV-based interview for ESSENCE, in connection with the twins' ninth or twelfth birthday. Diagnoses of febrile seizures (n = 492) and epilepsy (n = 282) were based on data from the Swedish National Patient Register. Prevalence of ESSENCE in individuals with febrile seizures and epilepsy was compared with prevalence in the twin population without seizures. The association between febrile seizures and ESSENCE was considered before and after adjustment for epilepsy. Age of diagnosis of febrile seizures and epilepsy was considered as a possible correlate of ESSENCE in febrile seizures and epilepsy. ResultsThe rate of ESSENCE in febrile seizures and epilepsy was significantly higher than in the total population without seizures (all P < 0.001). After adjusting for epilepsy, a significant association between febrile seizures and autism spectrum disorder, developmental coordination disorder, and intellectual disability remained. Earlier age of onset was associated with all ESSENCE except attention-deficit/hyperactivity disorder in epilepsy but not with ESSENCE in febrile seizures. ConclusionsIn a nationally representative sample of twins, there was an increased rate of ESSENCE in childhood epilepsy and in febrile seizures. Febrile seizures alone could occur as a marker for a broader ESSENCE phenotype.

Genetic and environmental aspects in the association between attention-deficit hyperactivity disorder symptoms and binge-eating behavior in adults: a twin study.

Prior research demonstrated that attention-deficit hyperactivity disorder (ADHD) is associated with binge-eating behavior, binge-eating disorder (BED), and bulimia nervosa (BN). The aim of this study was to investigate these associations in an adult twin population, and to determine the extent to which ADHD symptoms and binge-eating behavior share genetic and environmental factors. We used self-reports of current ADHD symptoms and lifetime binge-eating behavior and associated characteristics from a sample of over 18 000 adult twins aged 20-46 years, from the population-based Swedish Twin Registry. Mixed-effects logistic regression was used to examine the association between ADHD and lifetime binge-eating behavior, BED, and BN. Structural equation modeling was used in 13 773 female twins to determine the relative contribution of genetic and environmental factors to the association between ADHD symptoms and binge-eating behavior in female adult twins. ADHD symptoms were significantly associated with lifetime binge-eating behavior, BED, and BN. The heritability estimate for current ADHD symptoms was 0.42 [95% confidence interval (CI) 0.41-0.44], and for lifetime binge-eating behavior 0.65 (95% CI 0.54-0.74). The genetic correlation was estimated as 0.35 (95% CI 0.25-0.46) and the covariance between ADHD and binge-eating behavior was primarily explained by genetic factors (91%). Non-shared environmental factors explained the remaining part of the covariance. The association between adult ADHD symptoms and binge-eating behavior in females is largely explained by shared genetic risk factors.

Perinatal Outcome in Relation to Chorionicity in Twin Pregnancy

The incidence of multiple gestations is increasing worldwide and many studies have shown higher perinatal morbidity and mortality rates in monochorionic twins compared to dichorionic. The aim of this study was to assess the twin population born at a tertiary center and to evaluate the impact of chorionicity on perinatal outcomes of twin pregnancies. Retrospective study of all twins born in a tertiary center from January 2004 to December 2013. In this period, 1051 twins were born, related to 540 gestations (26.7% monochorionic; 73.3% dichorionic). There was no statistical significant difference between the groups concerning obstetric complications. The monochorionic group had a higher incidence of intrauterine growth restriction (20.5 vs 11.3%, p < 0.001), lower mean maternal age (29.9 vs 31.9 years, p < 0.001), lower mean gestational age (33.4 vs 34.3 weeks, p < 0.05) and lower mean birth weight (1943 vs 2147 g, p < 0.001). Monochorionic twins had a higher incidence of hyaline membrane disease (7 vs 4%, p < 0.05), sepsis (10.3 vs 5.8%, p < 0.05) and anemia (9.5 vs 5.4%, p < 0.05). There were no statistical significant differences concerning necrotizing enterocolitis, intraperiventricular hemorrhage or retinopathy of prematurity. Perinatal mortality was higher in the monochorionic group (5.2 vs 2.9%, p < 0.05). Monochorionic twins represent considerable challenges to both obstetricians and neonatologists and should be monitored and delivered at tertiary centers. Currently gemelarity has a major impact on total births. It would be interesting to develop protocols to standardize clinical approach to twins.

Concordance Rates of Adolescent Idiopathic Scoliosis in a Danish Twin Population.

Clinical, radiological, and genetic determination of zygosity of twin pairs from the Danish Twin Registry who self-reported having adolescent idiopathic scoliosis (AIS). To establish concordance rates of AIS. The etiology of and the true mode of inheritance of AIS remain unclear. Studies on concordance in twin pairs provide a basis for analyzing the influence of genetic versus environmental factors. In 2007, using self-report of AIS from the Danish Twin Registry, concordance rates of 0.13 in monozygotic twins and 0.00 in dizygotic twins were reported. All 46,418 twins registered in the Danish Twin Registry born from 1931 to 1982 were sent a survey, which included questions about scoliosis. The survey was returned by 34,944 individuals (75.3%) representing 23,204 pairs. From the present study, 548 individuals representing 274 complete twin pairs in which at least one twin self-reported having scoliosis were invited to a clinical and radiological examination. Zygosity was established by genetic testing. A total of 182 individuals (33.2%) of the original cohort agreed to participate, 128 of whom had scoliosis by self-report. There were 91 twin pairs, in which one or both twins had reported scoliosis and 36 individuals whose twin did not want to participate. Only 35 (27%) of the 128 participants with self-reported scoliosis had a clinically and radiologically confirmed curve. Calculating concordance in twins with Cobb angles greater than 10°, we found that the pairwise concordance rate was 0.4 (0.10-0.70) for monozygotic and 0.05 (-0.05-0.15) for dizygotic twins, P = 0.05, probandwise concordance was 0.45 (0.16-0.74) for monozygotic and 0.1 (-0.03-0.23) for dizygotic pairs. Concordance rates in a Danish twin population using genetic testing for zygosity are higher than previously reported using self-report. Although not statistically significant, the differences in monozygotic and dizygotic pairs indicate that genetic factors may be of importance for scoliosis. 3.

Filaggrin gene loss-of-function mutations explain discordance of atopic dermatitis within dizygotic twin pairs.

This study was designed to examine the association between loss-of-function mutations in the filaggrin gene (FLG) and atopic dermatitis (AD) and asthma in adult twins. A previously well-characterized cohort of 575 adult twins were genotyped for the loss-of-function mutations in FLG (R501X, 2282del4 and R2447X) most common among northern Europeans. Subjects were examined for symptoms of atopic diseases as well as for lung function, airway responsiveness, and atopy. In the whole population of twins, the risk for AD was significantly increased in individuals with FLG mutations in comparison with wild-type carriers (34.3% vs. 21.8%) after adjustment for possible confounders (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.07-3.41; P = 0.028). A significant association was also observed for persistent AD (OR 2.10, 95% CI 1.02-4.36; P = 0.046). There were no significant differences in risk for asthma by FLG mutation status in individuals with and without AD, respectively (P-value for interaction, 0.595). In 11 dizygotic twin pairs discordant for FLG mutation status, risk for AD was higher in the twin carrying the FLG mutation (five of 11 [45.5%] twins had developed AD) than in the non-carrier co-twin (two of 11 [18.2%] twins had developed AD) (OR 2.50, 95% CI 0.45-13.85; P = 0.293). FLG status did not explain a significant proportion of the variation in AD (P = 0.328) or asthma (P = 0.321). Filaggrin gene mutations are risk factors for the presence and persistence of AD and explain the discordance of AD within dizygotic twin pairs.

Association of Psoriasis With the Risk for Type 2 Diabetes Mellitus and Obesity.

Psoriasis has been shown to be associated with overweight and type 2 diabetes mellitus. The genetic association is unclear. To examine the association among psoriasis, type 2 diabetes mellitus, and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) in twins. This cross-sectional, population-based twin study included 34 781 Danish twins, 20 to 71 years of age. Data from a questionnaire on psoriasis was validated against hospital discharge diagnoses of psoriasis and compared with hospital discharge diagnoses of type 2 diabetes mellitus and self-reported BMI. Data were collected in the spring of 2002. Data were analyzed from January 1 to October 31, 2014. Crude and adjusted odds ratios (ORs) were calculated for psoriasis in relation to type 2 diabetes mellitus, increasing BMI, and obesity in the whole population of twins and in 449 psoriasis-discordant twins. Variance component analysis was used to measure genetic and nongenetic effects on the associations. Among the 34 781 questionnaire respondents, 33 588 with complete data were included in the study (15 443 men [46.0%]; 18 145 women [54.0%]; mean [SD] age, 44.5 [7.6] years). After multivariable adjustment, a significant association was found between psoriasis and type 2 diabetes mellitus (odds ratio [OR], 1.53; 95% CI, 1.03-2.27; P = .04) and between psoriasis and increasing BMI (OR, 1.81; 95% CI, 1.28-2.55; P = .001 in individuals with a BMI>35.0). Among psoriasis-discordant twin pairs, the association between psoriasis and obesity was diluted in monozygotic twins (OR, 1.43; 95% CI, 0.50-4.07; P = .50) relative to dizygotic twins (OR, 2.13; 95% CI, 1.03-4.39; P = .04). Variance decomposition showed that additive genetic factors accounted for 68% (95% CI, 60%-75%) of the variance in the susceptibility to psoriasis, for 73% (95% CI, 58%-83%) of the variance in susceptibility to type 2 diabetes mellitus, and for 74% (95% CI, 72%-76%) of the variance in BMI. The genetic correlation between psoriasis and type 2 diabetes mellitus was 0.13 (-0.06 to 0.31; P = .17); between psoriasis and BMI, 0.12 (0.08 to 0.19; P < .001). The environmental correlation between psoriasis and type 2 diabetes mellitus was 0.10 (-0.71 to 0.17; P = .63); between psoriasis and BMI, -0.05 (-0.14 to 0.04; P = .44). This study determines the contribution of genetic and environmental factors to the interaction between obesity, type 2 diabetes mellitus, and psoriasis. Psoriasis, type 2 diabetes mellitus, and obesity are also strongly associated in adults after taking key confounding factors, such as sex, age, and smoking, into account. Results indicate a common genetic etiology for psoriasis and obesity.

Analysis of the validity of assumptions underlying a research on the heritability of quantitative traits.

Heritability is a statistical measure, expressing the proportion of phenotypic variance that is explained by the genetic variance. Heritability of a given trait can vary in time and may differ between populations, which is inter alia associated with interactions and correlations between genotype and environment or population-specific differences. Therefore, heritability measures are modulated by both genetic and environmental factors. Twin studies constitute one of the methods used to determine contributions of genes and environment to a given trait. However, studies of this type suffer from some methodological limitations and require certain conditions to be satisfied; both these factors were analyzed in the present study. The studied material, including 1,263 pairs of male and female twins (among them 424 pairs of monozygotic twins and 839 pairs of dizygotic twins), born between the 22nd and 41st week of gestation, was collected at the Department of Perinatology and Gynecology, Poznan University of Medical Sciences, between 2002 and 2009. We analyzed the variance of six somatic traits. The contribution of genetic factors to the phenotypic variance of the studied twin population was estimated on the basis of the two heritability measures. Failure to meet the assumption of additivity of genetic and environmental effects probably is the cause of high values of heritability coefficients documented in our study. Analyzing the phenotypic variance of a trait, one cannot ignore the role of genotype-environment interactions and covariance, as these are their effects which increase the genetic variance and related coefficients of heritability. Therefore, it can be concluded that the genotypic component of the phenotypic variance of the trait is potentiated by the effects of various environmental factors. Our study confirmed that the critical remarks regarding the methodology of heritability estimation are fully justified. Consequently, the heritability indices of somatic traits should be considered only a provisional measure of genetic polymorphism, expressing an estimated relative contribution of genotypic variance to the phenotypic variance of a given trait.

Genetic and environmental influence on thyroid gland volume and thickness of thyroid isthmus: a twin study.

Decreased thyroid volume has been related to increased prevalence of thyroid cancer. One hundred and fourteen Hungarian adult twin pairs (69 monozygotic, 45 dizygotic) with or without known thyroid disorders underwent thyroid ultrasound. Thickness of the thyroid isthmus was measured at the thickest portion of the gland in the midline using electronic calipers at the time of scanning. Volume of the thyroid lobe was computed according to the following formula: thyroid height*width*depth*correction factor (0.63). Age-, sex-, body mass index- and smoking-adjusted heritability of the thickness of thyroid isthmus was 50% (95% confidence interval [CI], 35 to 66%). Neither left nor right thyroid volume showed additive genetic effects, but shared environments were 68% (95% CI, 48 to 80%) and 79% (95% CI, 72 to 87%), respectively. Magnitudes of monozygotic and dizygotic co-twin correlations were not substantially impacted by the correction of covariates of body mass index and smoking. Unshared environmental effects showed a moderate influence on dependent parameters (24-50%). Our analysis support that familial factors are important for thyroid measures in a general twin population. A larger sample size is needed to show whether this is because of common environmental (e.g. intrauterine effects, regional nutrition habits, iodine supply) or genetic effects.

A Swedish Population-Based Multivariate Twin Study of Externalizing Disorders

In epidemiological and twin populations, prior interview studies have identified an externalizing spectrum of disorders. Could this be detected utilizing objective registry data? In 20,603 twin pairs from the Swedish Twin Registry, we obtained information from national medical, criminal and pharmacy records on drug abuse (DA), criminal behavior (CB) and alcohol use disorders (AUD). Multivariate twin modeling was performed with the OpenMx package. A common pathway model with quantitative but not qualitative sex effects fit best with twin resemblance for the latent liability to externalizing syndromes due to both genetic and shared environmental factors. Heritability of the liability was higher in females (76 vs. 62%) while shared environmental influences were considerably stronger in males (23 vs. 3%). In both sexes, this latent liability was most strongly indexed by DA and least by CB. All three syndromes had specific genetic influences (especially CB and AUD in males, and CB in females) and specific shared environmental effects (especially DA and CB in males, and AUD in females). For DA, CB and AUD in men, and DA and AUD in women, at least 75% of the genetic risk arose through the common factor. The best fit model assumed that genetic and environmental influences on these externalizing syndromes in males and females were the same. We identified, in registry data, a highly heritable externalizing spectrum. DA, CB and AUD share substantial genetic and modest to moderate shared environmental influences. The nature of the externalizing spectrum differed meaningfully between the sexes.

Food Preference Patterns in a UK Twin Cohort.

Food liking-disliking patterns may strongly influence food choices and health. Here we assess: (1) whether food preference patterns are genetic/environmentally driven; and (2) the relationship between metabolomics profiles and food preference patterns in a large population of twins. 2,107 individuals from TwinsUK completed an online food and lifestyle preference questionnaire. Principle components analysis was undertaken to identify patterns of food liking-disliking. Heritability estimates for each liking pattern were obtained by structural equation modeling. The correlation between blood metabolomics profiles (280 metabolites) and each food liking pattern was assessed in a subset of 1,491 individuals and replicated in an independent subset of monozygotic twin pairs discordant for the liking pattern (65 to 88 pairs). Results from both analyses were meta-analyzed. Four major food-liking patterns were identified (Fruit and Vegetable, Distinctive Tastes, Sweet and High Carbohydrate, and Meat) accounting for 26% of the total variance. All patterns were moderately heritable (Fruit and Vegetable, h(2)[95% CI]: 0.36 [0.28; 0.44]; Distinctive Tastes: 0.58 [0.52; 0.64]; Sweet and High Carbohydrate: 0.52 [0.45, 0.59] and Meat: 0.44 [0.35; 0.51]), indicating genetic factors influence food liking-disliking. Overall, we identified 14 significant metabolite associations (Bonferroni p < 4.5 × 10(-5)) with Distinctive Tastes (8 metabolites), Sweet and High Carbohydrate (3 metabolites), and Meat (3 metabolites). Food preferences follow patterns based on similar taste and nutrient characteristics and these groupings are strongly determined by genetics. Food preferences that are strongly genetically determined (h(2) ≥ 0.40), such as for meat and distinctive-tasting foods, may influence intakes more substantially, as demonstrated by the metabolomic associations identified here.

The Influence of Chorion Type on Health Measures at Birth and Dental Development in Australian and Dutch Twins: A Comparative Study.

Chorion type may significantly influence the prenatal environment of twins. This study explored the associations between chorion type and gestational age, birth weight, birth length, and the timing of emergence of the first primary tooth in two populations of twins, Australian and Dutch. Additionally, we investigated the relationship between chorion type and birth weight discordance (BWD) in order to determine whether a significant relationship existed between discordance in birth weight and discordance in the timing of emergence of the first primary tooth. The two study samples consisted of 409 Australian twin pairs and 301 Dutch twin pairs, all of European ancestry. Data were collected through a combination of questionnaires and recording charts administered to the parents and through linkage with biological databases. In the Australian sample, monozygotic monochorionic (MZMC) twins experienced the shortest mean gestation time (35 weeks), the lowest mean birth length (46 cm) and the lowest mean birth weight (2.3 kg) compared with other twin groups. For the same variables in the Dutch sample, these trends with MZMC twinning were not observed. Chorion type did not significantly affect the mean timing of emergence of the first primary tooth in either sample. Monochorionicity was found to be significantly associated with BWD in both samples, but there was a significant association between BWD in MZMC twin pairs and timing of emergence of the first primary tooth only in the Australian sample. Results from this study support previous findings that the timing of emergence of the first primary tooth is influenced strongly by genetic factors and is well protected from environmental disturbances.