Low weight at birth has previously been shown to be associated with a number of adult diseases such as type 2 diabetes, cardiovascular disease, high blood pressure, and obesity later in life. Genome-wide association studies (GWAS) have been published for singleton-born individuals, but the role of genetic variation in birth weight (BW) in twins has not yet been fully investigated. A GWAS was performed in 4,593 female study participants with BW data available from the TwinsUK cohort. A genome-wide significant signal was found in chromosome 9, close to the NTRK2 gene (OMIM: 600456). QIMR, an Australian twin cohort (n = 3,003), and UK-based singleton-birth individuals from the Hertfordshire cohort (n = 2,997) were used as replication for the top two single nucleotide polymorphism (SNPs) underpinning this signal, rs12340987 and rs7849941. The top SNP, rs12340987, was found to be in the same direction in the Australian twins and in the singleton-born females (fixed effects meta-analysis beta = -0.13, SE = 0.02, and p = 1.48 × 10−8) but not in the singleton-born males tested. These findings provide an important insight into the genetic component of BW in twins who are normally excluded due to their lower BW when compared with singleton births, as well as the difference in BW between twins. The NTRK2 gene identified in this study has previously been associated with obesity.

Aiming to perform the first sociological survey of Hungarian twins, our main question was whether being a twin has positive consequences on one's life. Adult twins completed our questionnaire at three Hungarian summer twin festivals, in hospitals during medical twin studies, and on some websites online. Data represent 140 twin pairs (mean age: 38.2 ± 14.6 years). We employed some indices for measuring the resource nature of twinship. Three main types of benefits were distinguished: profit of attraction, as ‘material capital’; the easier obtainability of cultural goods when twins take part in it, as ‘cultural capital’; and positive aspects of an a priori existing dyadic relation, as ‘relational capital’. We were interested in the difference among types of twins regarding advantages. We paid special attention to the five groups of twins derived from gender and zygosity (i.e., monozygotic females, monozygotic males, dizygotic females, dizygotic males, opposite-sex pairs). Our analysis showed that Hungarian twins involved in our research basically enjoy their twinship; during their lives they used and still make use of different benefits given by it. In our twin samples, women had more advantages from being a twin than men. Significant differences could be observed on all indicators between monozygotic and dizygotic twins.

The aim of this study was to determine heritability estimates of treatment responses to a 10% hydrogen peroxide strip-based whitening system in twins. Eighty-five twin pairs were randomly assigned to 10% hydrogen peroxide whitening strips or placebo strips without peroxide. Both twins (monozygotic or dizygotic) received the same treatment. Maxillary teeth were treated for 30 minutes twice daily for 7 days. Efficacy was measured objectively as L* (light–dark), a* (red–green), and b* (yellow–blue) color change from digital images at baseline (∆) and day 8. Heritability estimates for tooth whitening treatment responses for changes from day 8 to baseline were obtained using variance-component methodologies. Whitening treatment responses were highly heritable (h2 = 71.0) for ∆b* and ∆a*(p < .0001), but not for ∆L* (h2 = 27.0), which was essentially modulated by environmental factors. This study has demonstrated that both genetic and environmental factors significantly contributed to seven-day whitening treatment responses achieved with 10% hydrogen peroxide strips.

Genetic and environmental contributions to preferences for rational and experiential thinking were examined in 100 pairs of monozygotic and 73 pairs of same-sex dizygotic Australian twins. Univariate analyses for experiential thinking and working memory capacity (WMC) revealed genetic effects accounted for 44% and 39% of the variability respectively, with non-shared environmental effects accounting for the balance. For rational thinking, the univariate models produced ambiguous results about the relative roles of heritability and shared environment, but a subsequent Cholesky analysis suggested genetic effects accounted for 34%, with the balance, 66%, explained by the non-shared environment. The Cholesky analysis revealed that shared genetic effects accounted for 60%, and non-shared environment accounted for 40% of the relationship between preference for rational thinking and WMC.

Recent studies report a correlation between excision repair cross-complementing group 2 (ERCC2) Lys751Gln polymorphism and an increased risk of lung cancer, but results are controversial and inconclusive. Thus, we conducted a comprehensive meta-analysis in order to assess the correlation between them. Our study uses an odds ratio (OR) with a 95% confidence interval (95% CI) to evaluate the strength of the association; we also performed Begg's funnel plot and the Egger's test to assess the publication bias of previous articles. Finally, our meta-analysis is comprised of 28 full studies, including 23,370 subjects (10,242 cases and 13,128 controls). Our overall research shows that ERCC2 Lys751Gln polymorphism carries an increased risk of developing lung cancer (C vs. A: OR = 1.160, 95% CI = 1.081–1.245, p = .000; CC vs. AA: OR = 1.252, 95% CI = 1.130–1.388, p = .000; CA vs. AA: OR = 1.152, 95% CI = 1.060–1.252, p = .001; CC+CA vs. AA: OR = 1.186, 95% CI = 1.089–1.292, p = .000; CC vs. CA+AA: OR = 1.196, 95% CI = 1.087–1.316, p = .000). In ethnic subgroup analyses, we find a significant risk among Caucasians (C vs. A: OR = 1.106, 95% CI = 1.048–1.166, p = .000; CC vs. AA: OR = 1.233, 95% CI = 1.103–1.378, p = .000; CC+CA vs. AA: OR = 1.113, 95% CI = 1.033–1.199, p = .005; CC vs. CA+AA: OR = 1.185, 95% CI = 1.069–1.313, p = .001) and among Asians under two genetic models (CA vs. AA: OR = 1.265, 95% CI = 1.034–1.549, p = .023; CC+CA vs. AA: OR = 1.252, 95% CI = 1.015–1.544, p = .036). These results were confirmed by similar findings, demonstrated by stratified analyses in study design and histological typing. This meta-analysis indicates that ERCC2 Lys751Gln polymorphism may lead to an increased susceptibility to lung cancer risk among Caucasians and Asians.

This study investigated the relationship between twin language, twins’ close ties, and social competence in a prospective longitudinal study. We hypothesized that twins whose tie is close would be more likely to develop a twin language, and these twins would be less likely to develop social competence. In addition, we hypothesize that some environmental factors, such as having an older sibling, preschool attendance, zygosity, and sex are also related to twin language, twins’ close ties, and social competence. At baseline in 1999 a mailed questionnaire survey was conducted, and a follow-up questionnaire was distributed in 2004 among 958 mothers. As a result, 516 respondents returned the questionnaire (53.9%). In this study, we used 261 twin pairs aged from 6 to 12 years (school-age children) for analysis, excluding those with missing values. In the present study, we found that zygosity and sex were associated with twins’ close ties. Having an older sibling and preschool attendance did not affect the twins’ close tie, twin language, or social competence. One of the most important findings was that social competence was not affected directly by twins’ close tie, but was affected when a twin language was found.

Valvular heart disease is a multifactorial disorder. Twin studies may help to better understand both genetic and environmental determinants contributing to the development of valve lesions. We describe the case of a 45-year-old female asymptomatic triplet with multiple valvular heart lesions, with a somewhat different pattern between the dizygotic twin pairs compared with the monozygotic twin pair. After thorough assessment of medical history and physical examination, the triplet underwent two- and three-dimensional transthoracic and transesophageal echocardiographic examinations to assess the pathomechanism and severity of their heart valve lesions. The monozygotic twin pair (second-born twin B and third-born twin C) showed the same pattern of valvular lesions: mild mitral, tricuspidal, and aortic regurgitation of the same pathomechanism (posterior mitral valve cleft and aortosclerosis). Interestingly, the examination of first-born twin (twin A), who was dizygotic to twins B and C, revealed mild protosystolic mitral and mild tricuspidal regurgitation, but neither aortic insufficiency nor mitral cleft or indentation could be detected. Beyond the genetic effect, we presume that the intrauterine twinning process might also play a role in the development of congenital valvular heart disease. In order to verify this, further investigation should be performed on larger twin populations. Nevertheless, when one twin is affected, the other asymptomatic twin should also be examined for valvular heart disease.

Studies on the determinants of physical activity have traditionally focused on social factors and environmental barriers, but recent research has shown the additional importance of biological factors, including genetic variation. Here we review the major tenets of this research to arrive at three major conclusions: First, individual differences in physical activity traits are significantly influenced by genetic factors, but genetic contribution varies strongly over age, with heritability of leisure time exercise behavior ranging from 27% to 84% and heritability of sedentary behaviors ranging from 9% to 48%. Second, candidate gene approaches based on animal or human QTLs or on biological relevance (e.g., dopaminergic or cannabinoid activity in the brain, or exercise performance influencing muscle physiology) have not yet yielded the necessary evidence to specify the genetic mechanisms underlying the heritability of physical activity traits. Third, there is significant genetic modulation of the beneficial effects of daily physical activity patterns on strength and endurance improvements and on health-related parameters like body mass index. Further increases in our understanding of the genetic determinants of sedentary and exercise behaviors as well as the genetic modulation of their effects on fitness and health will be key to meaningful future intervention on these behaviors.

Background: Previous genome-wide association studies (GWAS) have identified a large number of genetic variants for obesity and its related traits, representing a group of potential key genes in the etiology of obesity. Emerging evidence suggests that epigenetics may play an important role in obesity. It has not been explored whether the GWAS-identified loci contribute to obesity through epigenetics (e.g., DNA (deoxyribonucleic acid) methylation) in addition to genetics. Method: A multi-stage cross-sectional study was designed. We did a literature search and identified 117 genes discovered by GWAS for obesity and its related traits. Then we analyzed whether the methylation levels of these genes were also associated with obesity in two genome-wide methylation panels. We examined an initial panel of seven adolescent obese cases and seven age-matched lean controls, followed by a second panel of 48 adolescent obese cases and 48 age- and gender-matched lean controls. The validated CpG sites were further replicated in two independent replication panels of youth (46 vs. 46 and 230 cases vs. 413 controls, respectively) and a general population of youth, including 703 healthy subjects. Results: One CpG site in the lymphocyte antigen 86 (LY86) gene, which showed higher methylation in the obese in both the initial (p = .009) and second genome-wide DNA methylation panel (p = .008), was further validated in both replication panels (meta p = .00016). Moreover, in the general population of youth, the methylation levels of this region were significantly correlated with adiposity indices (p ≤ .02), insulin resistance (p = .001), and inflammatory markers (p < .001). Conclusion: By focusing on recent GWAS findings in genome-wide methylation profiles, we identified a solid association between LY86 gene DNA methylation and obesity.

Background: This study aims to assess whether the associations between burnout and sick leave due to stress-related mental disorders, other mental disorders, and somatic conditions are influenced by familial (genetic and shared environmental) factors. Methods: In this prospective cohort study, 23,611 Swedish twins born between 1959 and 1985, who answered a web-based questionnaire, including the Pines Burnout Measure 2004–2006, were included. Registry data on sick leave spells from the response date until December 31, 2010 were obtained from the Swedish Social Insurance Agency. Logistic regression analysis was performed to assess odds ratios with 95% confidence intervals for the association between burnout and sick leave for the whole sample, while conditional logistic regression of the same-sex discordant twin pairs was used to estimate the association between burnout and sick leave, adjusting for familial confounding. The Bivariate Cholesky models were used to assess whether the covariation between burnout and sick leave was explained by common genetic and/or shared environmental factors. Results: Burnout was a risk factor for sick leave due to stress-related and other mental disorders, and these associations were explained by familial factors. The phenotypic correlation between burnout and sick leave due to somatic conditions was 0.07 and the association was not influenced by familial factors. The phenotypic correlations between burnout and sick leave due to stress-related (0.26) and other mental disorders (0.30) were completely explained by common genetic factors. Conclusions: The association between burnout and sick leave due to stress-related and other mental disorders seems to be a reflection of a shared genetic liability.

Behavioral genetic research has been conducted at the University of Warsaw for the past 20 years. The work done at the University focuses primarily on the origins of individual differences in temperament and other personality traits. In particular, research is directed toward the traits postulated in the Regulative Theory of Temperament. We also focused on the heritability of socio-political attitudes, risk factors for human health, and post-traumatic stress disorder. The majority of the research that has been carried out is grounded in twin and family studies, although recent work based on molecular techniques has also been developed. This article reviews the most important directions and findings of behavioral genetics research at the University of Warsaw.

A twin design was used to examine the developmental nature of genetic, environmental, and phenotypic variations in hyperactivity and inattention problems (HIP). Mothers of 662 complete pairs of twins (273 monozygotic [MZ] pairs and 389 dizygotic [DZ] pairs) aged from 3 to 13 years (mean [SD] age = 8.3 [2.9] years) responded to the items of the HIP scale of the Strengths and Difficulties questionnaire via a telephone interview. Maximum likelihood MZ and DZ twin correlations in the total sample were 0.47 (95% CI: 0.37–0.55) and −0.01 (95% CI: −0.11–0.09). A standard univariate model incorporating age as a modifier was applied to the raw data. Results of model-fitting analyses showed that the phenotypic variation of HIP monotonically increased from age 3 to age 12 and that this increase was completely due to an increase in genetic variance, suggesting that it is genes that expand individual difference in ADHD symptoms with age during childhood. Child-specific environmental variance was constant during this age period. In terms of relative influences, total genetic factors increased from 33% (95% CI: 27–44%) at age 3 to 51% (95% CI: 28–71%) at age 13 and this increase was accompanied by a decrease in relative influences of child-specific environmental factors from 67% (95% CI: 56–73%) at age 3 to 49% (95% CI: 29–72%) at age 13. These estimates of genetic influences were somewhat lower than those found in most twin studies of ADHD symptoms. However, the increasing trend of genetic influences with age during childhood was consistent with the results of a recent meta-analysis of ADHD symptoms.

The management of twin pregnancies discordant for trisomy 21 is dependent on the gestation at diagnosis, chorionicity, and parental preference. Our experience with the management of 15 cases in 1,839 twin pregnancies over a 12-year period is described. Selective termination is not always associated with a successful outcome for the normal co-twin. Two of the three monochorionic twin pregnancies affected by trisomy 21 were discordant. Amniocentesis should be strongly considered rather than chorionic villus sampling in monochorionic twin pregnancies. Pregnancies that continue with a trisomy 21 affected fetus are at risk of polyhydramnios and premature labor.

We have evaluated copy number variants (CNVs) in six monozygotic twin pairs discordant for schizophrenia. The data from Affymetrix® Human SNP 6.0 arrays™ were analyzed using Affymetrix® Genotyping Console™, Partek® Genomics Suite™, PennCNV, and Golden Helix SVS™. This yielded both program-specific and overlapping results. Only CNVs called by Affymetrix Genotyping Console, Partek Genomics Suite, and PennCNV were used in further analysis. This analysis included an assessment of calls in each of the six twin pairs towards identification of unique CNVs in affected and unaffected co-twins. Real time polymerase chain reaction (PCR) experiments confirmed one CNV loss at 7q11.21 that was found in the affected patient but not in the unaffected twin. The results identified CNVs and genes that were previously implicated in mental abnormalities in four of the six twin pairs. It included PYY (twin pairs 1 and 5), EPHA3 (twin pair 3), KIAA1211L (twin pair 4), and GPR139 (twin pair 5). They represent likely candidate genes and CNVs for the discordance of four of the six monozygotic twin pairs for this heterogeneous neurodevelopmental disorder. An explanation for these differences is ontogenetic de novo events that differentiate in the monozygotic twins during development.

Length and weight in infancy are associated with neurodevelopment, but less is known about growth in other anthropometric measures. In this study we analyzed how the development in length, weight, head circumference, and chest circumference over infancy is associated with motor development in early childhood, using a twin study design. Information on physical development over infancy and the age at achievement of eight developmental milestones over early childhood was collected for 370 Japanese twin pairs. Linear mixed models were used to analyze how physical development is associated with motor development between individual twins, as well as within twin pairs, adjusting the results for shared maternal and postnatal environmental factors. Delayed motor development was associated with smaller body size over infancy, and we also found some suggestive evidence that it was associated with catch-up growth as well. When studying the associations within twin pairs discordant for motor development, similar associations were found. However, chest circumference showed the most robust association within discordant twin pairs. Smaller body size and rapid catch-up growth are associated with delayed motor development. When studying these associations within twin pairs and thus adjusting the results for gestational age as well as many other maternal and postnatal environmental factors, chest circumference showed the most robust association. Chest circumference, rarely used in developed countries, can offer additional information on prenatal conditions relevant for further motor development not achieved by more traditional anthropometric measures.

Epistasis is a growing area of research in genome-wide studies, but the differences between alternative definitions of epistasis remain a source of confusion for many researchers. One problem is that models for epistasis are presented in a number of formats, some of which have difficult-to-interpret parameters. In addition, the relation between the different models is rarely explained. Existing software for testing epistatic interactions between single-nucleotide polymorphisms (SNPs) does not provide the flexibility to compare the available model parameterizations. For that reason we have developed an R package for investigating epistatic and penetrance models, Epi2Loc, to aid users who wish to easily compare, interpret, and utilize models for two-locus epistatic interactions. Epi2Loc facilitates research on SNP–SNP interactions by allowing the R user to easily convert between common parametric forms for two-locus interactions, generate data for simulation studies, and perform power analyses for the selected model with a continuous or dichotomous phenotype. The usefulness of the package for model interpretation and power analysis is illustrated using data on rheumatoid arthritis.

Objective: The aim of this study was to assess fetal urinary production rates (FUPR) in twin gestations using 3D ultrasonography with VOCAL® (virtual organ computer-aided analysis) and to develop a curve of normal values for the target population. Methods: A cross-sectional study was performed in 30 normal twin pregnancies with gestational ages ranging from 20 to 34 weeks. FUPR was measured using a three-dimensional ultrasound (3D US) virtual organ computer-aided analysis (VOCAL) system. FUPR (ml/hour) was calculated during the filling phase using the equation UPR = (VFB2 - VFB1)/time. The values for UPR were plotted as a function of fetal biometry (biparietal diameter) to generate a nomogram. Results: A total of 41 normal twin fetuses with gestational ages between 20 and 34 weeks were investigated. Eleven were excluded because of inadequate bladder contour image quality and/or the observation of micturition in one or both fetuses. Linear regression analysis of FUPR as a function of biparietal diameter (BPD) shows the normal range for UPR by fetal biometry and is expressed by the following equation: Ln(UPR) = -5.0121 + 0.0548 BPD (R2 0.3386, p value <.001). There was no statistically significant difference when the UPR was stratified by chorionicity. Conclusions: The use of biometric parameters to predict fetal FUPR seems to be useful. In twin pregnancies, BPD is the variable that is most closely related to FUPR. For each 1 mm increase in BPD, there is a 5% increase in FUPR. Chorionicity did not affect FUPR.

We aimed to investigate the association between weight change from 20 years of age and insulin resistance (IR), and genetic and environmental relationships between these traits. In 594 Korean twins and family members (209 men, 385 women, 44.0 ± 10.8 years old), the percentage of weight change was calculated using self-reported body weight at 20 years of age and currently measured bodyweight. IR traits were assessed using fasting plasma glucose and insulin, the homeostasis model assessment of IR index (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI). Linear mixed analysis was applied after adjusting for household, body mass index (BMI) at the age of 20 years, age, sex, alcohol, smoking, physical activity, and caloric intake. Heritabilities and genetic and environmental correlations were estimated after adjusting for covariates. In 55 monozygotic twin pairs discordant for HOMA-IR level by >0.3, a conditional logistic regression analysis was conducted regarding weight change. Increases in glucose, insulin, and HOMA-IR and a decrease in QUICKI were associated with a higher percentage of weight change (p < .05). Estimated heritabilities for IR traits were 0.401–0.606 (p < .001). In cross-trait relationships, environmental correlations were -0.43–0.42 (p < .05 for all IR), while genetic correlations were -0.27–0.27 (p < .05 for QUICKI, insulin, and HOMA-IR). In 55 pairs of monozygotic twins, the odds ratio (95% confidence interval) for having a higher level of HOMA-IR was 1.10 (1.03–1.17) with 1% increase in weight change since 20 years old, after adjusting for lifestyle-related factors. In conclusion, both genetic and environmental influences played significant roles in the positive association between weight change from 20 years of age and IR.

Background: Recent studies have reported associations between air pollution exposure and neurodevelopmental disorders in children, but the role of pre- and postnatal exposure has not been elucidated. Aim: We aimed to explore the risk for autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) among children in relation to pre- and postnatal exposure to air pollution from road traffic. Methods: Parents of 3,426 twins born in Stockholm during 1992–2000 were interviewed, when their children were 9 or 12 years old, for symptoms of neurodevelopmental disorders. Residence time-weighted concentrations of particulate matter with a diameter <10 μm (PM10) and nitrogen oxides (NOx) from road traffic were estimated at participants’ addresses during pregnancy, the first year, and the ninth year of life using dispersion modeling, controlling for seasonal variation. Multivariate regression models were used to examine the association between air pollution exposure and neurodevelopmental outcomes, adjusting for potential confounding factors. Results: No clear or consistent associations were found between air pollution exposure during any of the three time windows and any of the neurodevelopmental outcomes. For example, a 5–95% difference in exposure to NOx during pregnancy was associated with odds ratios (ORs) of 0.92 (95% confidence interval (CI): 0.44–1.96) and 0.90 (95% CI: 0.58–1.40) for ASD and ADHD respectively. A corresponding range in exposure to PM10 during pregnancy was related to ORs of 1.01 (95% CI: 0.52–1.96) and 1.00 (95% CI: 0.68–1.47) for ASD and ADHD. Conclusions: Our data do not provide support for an association between pre- or postnatal exposure to air pollution from road traffic and neurodevelopmental disorders in children.

Our goal was to estimate genetic and environmental sources of influence on adolescent problematic internet use, and whether these individual differences can be explained by effortful control, an important aspect of self-regulation. A sample of 825 pairs of Chinese adolescent twins and their parents provided reports of problematic internet use and effortful control. Univariate analysis revealed that genetic factors explained 58–66% of variance in problematic internet use, with the rest explained by non-shared environmental factors. Sex difference was found, suggesting boys’ problematic internet use was more influenced by genetic influences than girls’ problematic internet use. Bivariate analysis indicated that effortful control accounted for a modest portion of the genetic and non-shared environmental variance in problematic internet use among girls. In contrast, among boys, effortful control explained between 6% (parent report) and 20% (self-report) of variance in problematic internet use through overlapping genetic pathways. Adolescent problematic internet use is heritable, and poor effortful control can partly explain adolescent problematic internet use, with effects stronger for boys. Implications for future research are discussed.