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Type 2 diabetes, which is caused by both genetic and environmental factors, may be diagnosed using the oral glucose tolerance test (OGTT). Recent studies demonstrated specific patterns in glucose curves during OGTT associated with cardiometabolic risk profiles. As the relative contribution of genetic and environmental influences on glucose curve patterns is unknown, we aimed to investigate the heritability of these patterns. We studied twins from the Danish GEMINAKAR cohort aged 18-67 years and free from diabetes at baseline during 1997-2000; glucose concentrations were measured three times during a 2-h OGTT. Heterogeneity of the glucose response during OGTT was examined with latent class mixed-effects models, evaluating goodness of fit by Bayes information criterion. The genetic influence on curve patterns was estimated using quantitative genetic modeling based on linear structural equations. Overall, 1455 twins (41% monozygotic) had valid glucose concentrations measured from the OGTT, and four latent classes with different glucose response patterns were identified. Statistical modeling demonstrated genetic influence for belonging to a specific class or not, with heritability estimated to be between 45% and 67%. During ∼12 years of follow-up, the four classes were each associated with different incidence of type 2 diabetes. Hence, glucose response curve patterns associated with type 2 diabetes risk appear to be moderately to highly heritable. [ABSTRACT FROM AUTHOR]

The Danish Twin Registry (DTR) was established in the 1950s, when twins born from 1870 to 1910 were ascertained, and has since been extended to include twins from birth cohorts until 2009. The DTR currently comprises of more than 175,000 twins from the 140 birth cohorts. This makes the DTR the oldest nationwide twin register and among the largest in the world. The combination of data from several surveys, including biological samples and repeated measurements on the same individuals, and data from Danish national registers provides a unique resource for a wide range of twin studies. This article provides an updated overview of the data in the DTR: First, we provide a summary of the establishment of the register, the different ascertainment methods and the twins included; then follows an overview of major surveys conducted in the DTR since 1994 and a description of the DTR biobank, including a description of the molecular data created so far; finally, a short description is given of the linkage to Danish national registers at Statistics Denmark and some recent examples of studies using the various data resources in the DTR are highlighted. [ABSTRACT FROM AUTHOR]

The Nordic countries have comprehensive, population-based health and medical registries linkable on individually unique personal identity codes, enabling complete long-term follow-up. The aims of this study were to describe the NorTwinCan cohort established in 2010 and assess whether the cancer mortality and incidence rates among Nordic twins are similar to those in the general population. We analyzed approximately 260,000 same-sexed twins in the nationwide twin registers in Denmark, Finland, Norway and Sweden. Cancer incidence was determined using follow-up through the national cancer registries. We estimated standardized incidence (SIR) and mortality (SMR) ratios with 95% confidence intervals (CI) across country, age, period, follow-up time, sex and zygosity. More than 30,000 malignant neoplasms have occurred among the twins through 2010. Mortality rates among twins were slightly lower than in the general population (SMR 0.96; CI 95% [0.95, 0.97]), but this depends on information about zygosity. Twins have slightly lower cancer incidence rates than the general population, with SIRs of 0.97 (95% CI [0.96, 0.99]) in men and 0.96 (95% CI [0.94, 0.97]) in women. Testicular cancer occurs more often among male twins than singletons (SIR 1.15; 95% CI [1.02, 1.30]), while cancers of the kidney (SIR 0.82; 95% CI [0.76, 0.89]), lung (SIR 0.89; 95% CI [0.85, 0.92]) and colon (SIR 0.90; 95% CI [0.87, 0.94]) occur less often in twins than in the background population. Our findings indicate that the risk of cancer among twins is so similar to the general population that cancer risk factors and estimates of heritability derived from the Nordic twin registers are generalizable to the background populations. [ABSTRACT FROM AUTHOR]

Background: Hall (Embryologic development and monozygotic twinning. Acta Geneticae Medicae et Gemellologiae, Vol. 45, 1996, pp. 53-57) hypothesized that chromosomal aberrations can lead to monozygotic (MZ) twinning. However, twinning and chromosomal aberrations increase prenatal mortality and could reduce the prevalence of chromosomal aberrations in live-born twins. We compared prevalence proportion ratios (PPR) of chromosomal aberrations and trisomy 21 (T21) in live-born twins versus singletons born in Denmark during 1968-2009.Methods: We linked the Danish Twin Registry and a 5% random sample of all singletons to the Danish Cytogenetic Central Register and calculated PPR adjusted for maternal age for MZ, dizygotic (DZ), and all twins versus singletons. Zygosity was based on questionnaires or genetic markers.Results: No overall difference in risk of chromosomal aberrations or T21 in twins versus singletons was found. PPR in MZ and DZ twins was 0.87 (95% CI [0.60, 1.27]) and 1.05 (95% CI [0.88, 1.27]), respectively. For T21 there was a tendency to a lower prevalence in MZ twins compared to singletons (PPR: 0.29, 95% CI [0.07, 1.14]), whereas PPR was significantly increased in DZ twins (1.62, 95% CI [1.20, 2.19]). The observed proportion of MZ twin pairs among twin pairs with aberrations (0.22, 95% CI [0.16, 0.28]) was significantly lower than the proportion expected from the Weinberg method (0.32, 95% CI [CI, 0.26, 0.39]).Conclusion: Based on databases providing complete national coverage on twins with chromosomal aberrations, we found no overall difference in risk of chromosomal aberrations or T21 in twins versus singletons. Around conception twins may have an increased risk of chromosomal aberrations, but loss of especially MZ embryos could lead to similar risk among live-born twins and singletons. [ABSTRACT FROM AUTHOR]

Avoiding overeating and being physically active is associated with healthy aging, but methodological issues challenge the quantification of the association. Intrapair comparison of twins is a study design that attempts to minimize social norm-driven biased self-reporting of lifestyle factors. We aimed to investigate the association between self-reported lifestyle factors and subsequent survival in 347 Danish twin pairs aged 70 years and older and, additionally, to investigate the reliability of these self-reports. The twins were interviewed in 2003 and followed for mortality until 2015. They were asked to compare their appetite and physical activity to that of their co-twins in different stages of life. On an individual level, we found a positive association between current self-reported physical activity and late-life survival for elderly twins. This was supported by the intrapair analyses, which revealed a positive association between midlife and current physical activity and late-life survival. A positive association between lower appetite and late-life survival was found generally over the life course in the individual level analyses but not in the intrapair analyses. Kappa values for the inter-twin agreement on who ate the most were 0.16 to 0.34 in different life stages, and for physical activity 0.19 to 0.26, corresponding to a slight-to-fair agreement. Approximately, 50% of the twin pairs were not in agreement regarding physical activity, and of these twins 75% (95% CI: 67–82%) considered themselves the most active twin. These findings indicate a still-existing tendency of answering according to social norms, even in a twin study designed to minimize this. [ABSTRACT FROM PUBLISHER]

Sex differences in religion are well known, with females generally being more religious than males, and shared environmental factors have been suggested to have a large influence on religiousness. Twins from opposite-sex (OS) and same-sex (SS) pairs may differ because of a dissimilar psycho-social rearing environment and/or because of different exposures to hormones in utero. We hypothesized that OS females may display more masculine patterns of religiousness and, vice versa, that OS males may display more feminine patterns. We used a web-based survey conducted in Denmark, which is a secular society. The survey included 2,997 twins aged 20–40 years, identified through the population-based Danish Twin Registry. We applied la Cour and Hvidt's adaptation of Fishman's three conceptual dimensions of meaning: Cognition, Practice, and Importance, and we used Pargament's measure of religious coping (RCOPE) for the assessment of positive and negative religious coping patterns. Differences between OS and SS twins were investigated using logistic regression for each sex. The analyses were adjusted for dependence within twin pairs. No significant differences in religiousness and religious coping were found for OS and SS twins except that more OS than SS females were members of the Danish National Evangelical Lutheran Church and fewer OS than SS females were Catholic, Muslim, or belonged to other religious denominations. Moreover, OS males at age 12 had higher rates of church attendance than did SS males. This study did not provide evidence for masculinization of female twins with male co-twins with regard to religiousness. Nor did it show any significant differences between OS and SS males except from higher rates of church attendance in childhood among males with female co-twins. [ABSTRACT FROM PUBLISHER]

Over the last 60 years, the resources and the research in the Danish Twin Registry (DTR) have periodically been summarized. Here, we give a short overview of the DTR and a more comprehensive description of new developments in the twenty-first century. First, we outline our experience over the last decade of combining questionnaire and survey data with national demographic, social, and health registers in Statistics Denmark. Second, we describe our most recent data collection effort, which was conducted during the period 2008–2011 and included both in-person assessments of 14,000+ twins born 1931–1969 and sampling of biological material, hereby expanding and consolidating the DTR biobank. Third, two examples of intensively studied twin cohorts are given. The new developments in the DTR in the last decade have facilitated the ongoing research and laid the groundwork for new research directions. [ABSTRACT FROM AUTHOR]

We compare a recent Danish twin survey on political attitudes and behaviors to a nationally representative survey covering similar topics. We find very similar means and variances for most of our constructed scales of political attitudes and behaviors in the two surveys, although even small differences tend to be statistically significant due to sample size. This suggests that the twin study can be used to make inferences on the heritability of several political traits in the Danish population. [ABSTRACT FROM PUBLISHER]

We analyzed the association between mean height and old age cognition in two Nordic twin cohorts with different childhood living conditions. The cognitive performance of 4720 twin individuals from Denmark (mean age 81.6 years, SD = 4.59) and Finland (mean age 74.4 years, SD = 5.26) was measured using validated cognitive screens. Taller height was associated with better cognitive performance in Finland (β-estimates 0.18 SD/10cm, p value < .001, for men and 0.13 SD, p = .008, for women), but this association was not significant in Denmark (β-estimates 0.0093 SD, p value = .16, for men and 0.0075 SD, p value = .016, for women) when adjusted for age and education/social class. Among Finnish participants higher variability of cognitive performance within shorter height quintiles was observed. Analysis using gene-environment interaction models showed that environmental factors exerted a greater impact on cognitive performance in shorter participants, whereas in taller participants' it was explained mainly by genetic factors. Our results suggest that shorter participants with childhood adversity are more vulnerable to environmental risk factors for cognitive impairment. [ABSTRACT FROM PUBLISHER]

Few studies have examined differences of civil status of twins and singletons and the conclusions are contradictory. In the present study, based on a linkage between the Danish Twin Register, a random 5% sample of the total Danish population, and administrative register databases, the authors compare rates of marriage and divorce in a sample of 35,975 twins and 81,803 singletons born 1940-1964. Cox-regressions are used in order to control for potential confounders. We find that compared with singletons twins have significantly lower marriage rates: (males: 15-19 years: Hazard Ratio (HR) = 0.66 (95%CI: 0.58-0.76); 20-24 years: 0.85 (0.82-0.88); 25 years or more: 0.96 (0.93-0.98) and females: 15-19 years: 0.70 (0.67-0.75); 20-24 years: 0.83 (0.80-0.85); 25 years or more: 0.94 (0.91-0.97)). There is no difference in divorce rates for males, but a significantly lower divorce rate for female twins compared with singletons (HR=0.87, 95%CI: 0.83-0.90). These differences offset each other, thus 57% of both populations remain in their first marriage until censoring. The interpretation may be that since twins have a partner from birth, they do not have the same need for marriage as singletons but have more experience in maintaining a relationship if they do marry. [ABSTRACT FROM AUTHOR]

Bread is an elementary part of the western diet, and especially rye bread is regarded as an important source of fibre. We investigated the heritability of eating bread in terms of choice of white and rye bread and use-frequency of bread in female and male twins in Denmark and Finland. The study cohorts included 575 Danish (age range 18-67 years) and 2009 Finnish (age range 22-27 years) adult twin pairs. Self-reported frequency of eating bread was obtained by food frequency questionnaires. Univariate models based on linear structural equations for twin data were used to estimate the relative magnitude of the additive genetic, shared environmental and individual environmental effects on bread eating frequency and choice of bread. The analysis of bread intake frequency demonstrated moderate heritability ranging from 37-40% in the Finnish cohort and 23-26% in the Danish cohort. The genetic influence on intake of white bread was moderate (24-31%), while the genetic influence on intake of rye bread was higher in men (41-45%) than in women (24-33%). Environmental influences shared by the twins were not significant. Consumption of bread as well as choice of bread is influenced by genetic predisposition. Environmental factors shared by the co-twins (e.g., childhood environment) seem to have no significant effects on bread consumption and preference in adulthood. [ABSTRACT FROM AUTHOR]

Evidence of a positive association between birthweight and IQ has been established in several studies. Analyses of within twin pair differences in birthweight and IQ have been used to shed light on the basis of the association. The strength of this approach is the possibility of controlling for both unmeasured common childhood-environmental factors as well as genetic factors shared by the co-twins. Two twin studies suggest the existence of genetic mediation between birthweight and IQ, that is, common genetic factors influence both fetal growth and IQ in childhood, while two other twin studies find no evidence of such mediation. In the present study we use a large population-based national register study of 2,413 Danish twin-pairs from birth cohorts 1986-1990, of which we have zygosity information on 74%. We perform individual level as well as intra-pair analyses of birthweight and school achievements at age 16. For both sexes we observed a monotonic increase in academic performance with increasing percentiles of birthweight. However, we did not find that this association is due to genetic mediation. [ABSTRACT FROM AUTHOR]

Dizygotic twinning rates have changed over time, which has been seen as a sign of a decline in fecundity. Since a woman's birthweight has been shown to be a marker of her fecundity, maternal birthweight may correlate with subsequent twinning rates. In the Danish National Birth Cohort (1996-2002), we examined if maternal birthweight, and whether she was born at term or preterm, correlated with her probability of multiple birth. For 20,719 live born infants, we had self-reported information about maternal birthweight, collected during the first wave of the 7-year follow-up, and information on multiple births from record linkage. The association between maternal birthweight and multiple births was investigated by use of logistic regression and presented as odds ratios (ORs) with 95% confidence intervals (CIs). Compared to women born at term with a birthweight of 3001-4000 g, women with a birthweight > 4500 g appeared to have higher chance of multiple birth while women with a birthweight of 4001-4500 had a lower chance, especially if the analysis was restricted to women with a BMI < 25 (Adjusted ORs 2.3 [1.0-5.4] and 0.4 [0.2-0.9] respectively). Odds ratios for dizygotic twinning were of the same magnitude. In women with a BMI >or= 25, no obvious pattern was present. Our findings do not indicate that twinning is a fecundity indicator. Women with a birthweight that may indicate a pregnancy complicated with gestational diabetes had the highest rate of multiple birth. These findings are new and should be put to a critical test in other data sources. [ABSTRACT FROM AUTHOR]

Twinning rates have changed substantially over time for reasons that are only partly known. In this study we studied smoking, coffee and alcohol intake, and their possible interaction with obesity as potential determinants of twinning rates using data from the Danish National Birth Cohort between 1996 and 2002. We identified 82,985 pregnancies: 81,954 singleton and 1031 twins. For the twins we had data to classify 121 as monozygotic, 189 dizygotic (same sex), 313 dizygotic (opposite sex) but, 408 were of the same sex but with unknown zygosity. All mothers were interviewed about their prepregnancy weight and height, coffee and alcohol intake, smoking habits, and potential confounding factors at early stages of pregnancy. We identified smoking (> 10 cigarettes/day) as a possible determinant of twinning, particularly for dizygotic twinning rates (same sex) and furthermore corroborated that obesity and the mother's age are strong correlates of twinning. Others have found coffee intake to increase twinning rates but that is not seen in these data. [ABSTRACT FROM AUTHOR]

Although social and intellectual engagement have been consistently associated with late-life functioning, rather than true causation, these associations may reflect the experiential choices of high functioning individuals (i.e., selection effects). We investigated the association of social activity with late-life physical functioning, cognitive functioning, and depression symptomatology using data from 1112 pairs of like-sex twins who participated in the Longitudinal Study of Aging Danish Twins. Consistent with previous research, we found that social activity was significantly correlated with overall level of physical functioning, cognitive functioning, and depression symptomatology. We also found that social activity was significantly and moderately heritable (estimate of .36), raising the possibility that its association with late-life functioning might reflect selection processes. Further, social activity did not predict change in functioning and in monozygotic twin pairs discordant on level of social activity, the more socially active twin was not less susceptible to age decreases in physical and cognitive functioning and increases in depression symptomatology than the less socially active twin. These results are interpreted in the context of the additional finding that nonshared environmental factors, although apparently not social activity, are the predominant determinant of changes in late-life functioning. [ABSTRACT FROM AUTHOR]

The Danish Twin Registry is the oldest national twin register in the world, initiated in 1954, and, by the end of 2005, contained more than 75,000 twin pairs born in the between 1870 and 2004. The Danish Twin Registry is used as a source for studies on the genetic influence on normal variation in clinical parameters associated with the metabolic syndrome and cardiovascular diseases, clinical studies of specific diseases, and aging and age-related health problems. The combination of survey data, clinical data and linkage to national health-related registers enables follow-up studies of both the general twin population and twins from clinical studies. This paper summarizes the newest extension of the register and gives examples of new developments and phenotypes studied. [ABSTRACT FROM AUTHOR]

Irving I. Gottesman played an important role for psychiatric genetic research in Denmark through more than 40 years of collaboration with Danish scientists, resulting in important twin and family studies based upon the unique national registers available in Denmark. [ABSTRACT FROM AUTHOR]