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The ‘thrifty phenotype’ hypothesis proposed that fetal undernutrition increases risk of diabetes in later life. Undernourished low birthweight Indian babies are paradoxically more adipose compared to well-nourished European babies, and are at higher risk of diabetes in later life. Twin pregnancies are an example of in utero growth restrictive environment due to shared maternal nutrition. There are few studies of body composition in twins. We performed secondary analysis of anthropometric body composition of twins and singletons in Guinea-Bissau, an economically deprived African country.
Anthropometric data were available on 7–34 year-old twins (n = 209, 97 males) and singletons (n = 182, 86 males) in the Guinea-Bissau Twin Registry at the Bandim Health Project. Twins had lower birthweight (2420 vs 3100 g, p < 0.001); and at follow-up, lower height (HAZ mean Z-score difference, −0.21, p = 0.055), weight (WAZ −0.73, p = 0.024) and BMI (BAZ −0.22, p = 0.079) compared to singletons but higher adiposity (skinfolds: +0.33 SD, p = 0.001). Twins also had higher fasting (+0.38 SD, p < 0.001) and 2-hour OGTT glucose concentrations (+0.29 SD, p < 0.05). Linear mixed-effect model accounting for intrapair correlations and interactions confirmed that twins were thinner but fatter across the age range. Data on maternal morbidity and prematurity were not available in this cohort.
African populations are known to have a muscular (less adipose) body composition. Demonstration of a thin-fat phenotype in twins in a low socio-economic African country supports the thesis that it could be a manifestation of early life undernutrition and not exclusive to Indians. This phenotype could increase risk of diabetes and related conditions.
Leukocyte telomere length (LTL) is a widely hypothesized biomarker of biological aging. Persons with shorter LTL may have a greater likelihood of developing dementia. We investigate whether LTL is associated with cognitive function, differently for individuals without cognitive impairment versus individuals with dementia or incipient dementia.
Enrolled subjects belong to the Long Life Family Study (LLFS), a multi-generational cohort study, where enrollment was predicated upon exceptional family longevity. Included subjects had valid cognitive and telomere data at baseline. Exclusion criteria were age ≤ 60 years, outlying LTL, and missing sociodemographic/clinical information. Analyses were performed using linear regression with generalized estimating equations, adjusting for sex, age, education, country, generation, and lymphocyte percentage.
Older age and male gender were associated with shorter LTL, and LTL was significantly longer in family members than spouse controls (p < 0.005). LTL was not associated with working or episodic memory, semantic processing, and information processing speed for 1613 cognitively unimpaired individuals as well as 597 individuals with dementia or incipient dementia (p < 0.005), who scored significantly lower on all cognitive domains (p < 0.005).
Within this unique LLFS cohort, a group of families assembled on the basis of exceptional survival, LTL is unrelated to cognitive ability for individuals with and without cognitive impairment. LTL does not change in the context of degenerative disease for these individuals who are biologically younger than the general population.
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.
Sub-Saharan Africa has the highest natural twinning rate in the world. Unfortunately, due to lack of adequate care during pregnancy, labor and postnatally, twin mortality in Sub-Saharan Africa also remains very high. Thus, it has been estimated that one in five twins dies during the childhood years. In spite of this, surprisingly few twin studies have been conducted in the region, making additional epidemiological data much needed. In 2009, we established one of the first twin registries in Sub-Saharan Africa at the Bandim Health Project in Guinea-Bissau. The registry had two main objectives. First, we wanted to describe the twinning rate and mortality patterns among newborn twins, including mortality risk factors and hospitalization patterns. Such studies can help the local clinicians improve twin health by identifying the most vulnerable children. Second, and in light of the rapidly increasing diabetes rates in Africa, we wanted to use the registry to particularly focus on metabolic disorders. Twins are often born with low birth weight, which according to the ‘thrifty phenotype hypothesis’ could predispose them to metabolic disorders later in life. Yet, no such ‘fetal programming’ data have previously been available from African twins despite the fact that nutritional patterns and influences from other factors (e.g., infections) could be markedly different here compared to high-income settings. In this article, we summarize the findings and current status of the Guinea-Bissau twin registry.
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.
Individuals exposed to the same environmental factor show variation in responses and health outcomes. Such observations could be caused by chance or by gene-environment interactions – where gene variants modulate the effect of environmental factors on morbidity, aging and mortality or vice-versa. Twin and family studies have shown that lifespan is moderately heritable and that the chance of survival at the highest ages might be increasingly influenced by genetic factors. However, only for two genes, common variants have consistently been associated with longevity: the Apolipoprotein E gene and, to a lesser extent, FOXO. In this chapter, we review current knowledge on the association between Apolipoprotein E variants and mortality and summarize current evidence for interactions between lifestyle and Apolipoprotein E gene variants in morbidity, aging and longevity.
Can we make a copy of Tycho’s “De Nova Stella” that can in fact survive a nova? At first, this may seem at best a nerdish, if not distinctly foolish question. However, it is also both a technological and a philosophical question: in fact, answering questions like this is linked to both technical, physical and sociological problems related to the long-term preservation and curation of objects from current and past civilizations.
The undertaking presented here is two-fold: Firstly, we report on the results from a state-of the art short-term project, in which we have digitized and analysed three well-known rare books Pertain ing to astronomical observations by Tycho Brahe on the island of Hven. The project led to the creation of free e-books, enabling open access to the sky as recorded by Tycho.
Secondly, we discuss some long-term issues related to the digital and physical preservation of scientific knowledge and heritage in general, exemplified by e.g. the works by Tycho.
Future work includes further physical analysis of the books and fragments, a systematic extraction and digitization of the astronomical observations, digital curation and dissemination, as well as research into the possibility of creating representations and replicas of the works, durable on extremely long time-scales.
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.
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.
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.
A complex interrelation exists between change in depression symptomatology and cognitive decline. Studies indicate either that depression is a direct risk factor for cognitive change over time, or vice versa. Longitudinal twin studies provide the possibility to unravel cause and effect of correlated traits. Here, we have applied twin modeling approaches to shed light on the genetic correlation between both level and change of depression symptomatology and cognitive functioning, and to further explore the bidirectionality of any such correlation using assessments of both phenotypes at two occasions 10 years apart. The study included 2,866 Danish twins with a mean age of 56.8 years at intake (range: 45–68 years). Of these, 1,267 were intact pairs. A total number of 1,582 twins (55%), of whom 557 were intact pairs, participated in the follow-up survey. We found stable cross-sectional heritability estimates of approximately 60% for general cognitive abilities and 30% for affective depressive symptoms. There was a considerable decline in the mean cognitive performance over 10 years, whereas the mean affective depression symptoms score was stable and with no genetic contribution to any individual change. Additionally, we saw a small but significant cross-trait correlation at both occasions (-0.11 and -0.09, respectively), but cross-trait cross-occasion analysis revealed no evidence that either of the two traits predicts the other over a 10-year interval. Thus, our study was not able to detect any causal association between change in depressive symptomatology and cognitive decline in middle-aged and elderly people over a 10-year interval.
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.
Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9–11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9–13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47–0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61–78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
The genetic influences on aging-related phenotypes, including cognition and depression, have been well confirmed in the Western populations. We performed the first twin-based analysis on cognitive performance, memory and depression status in middle-aged and elderly Chinese twins, representing the world's largest and most rapidly aging population. The sample consisted of 384 twin pairs with a median age of 50 years. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) scale; memory was assessed using the revised Wechsler Adult Intelligence scale; depression symptomatology was evaluated by the self-reported 30-item Geriatric Depression (GDS-30)scale. Both univariate and multivariate twin models were fitted to the three phenotypes with full and nested models and compared to select the best fitting models. Univariate analysis showed moderate-to-high genetic influences with heritability 0.44 for cognition and 0.56 for memory. Multivariate analysis by the reduced Cholesky model estimated significant genetic (rG = 0.69) and unique environmental (rE = 0.25) correlation between cognitive ability and memory. The model also estimated weak but significant inverse genetic correlation for depression with cognition (-0.31) and memory (-0.28). No significant unique environmental correlation was found for depression with other two phenotypes. In conclusion, there can be a common genetic architecture for cognitive ability and memory that weakly correlates with depression symptomatology, but in the opposite direction.
It is well known that human behavior and individual psychological traits are moderately to substantially heritable. Over the past decade, an increasing number of studies have explored the genetic and environmental influence on religiousness. These studies originate predominantly from countries generally considered more religious than the very secular northern European countries. Comparisons of the results are complicated by diverse definitions of religiousness, but several studies indicate that the influence of the family environment is most predominant in early life, whereas genetic influences increase with age. We performed a population-based twin study of religiousness in a secular society using data from a Web-based survey sent to 6,707 Danish twins born 1970–1989, who were identified in the Danish Twin Registry. We applied Fishman's three conceptual dimensions of religiousness: cognition, practice, and importance. In all polygenic models and biometric analyses, we controlled for gender and age. The study sample comprised 2,237 same sex twins, a response rate of 45%. We found high correlations within both monozygotic and dizygotic twin pairs in most items of religiousness, indicating a large influence from shared environmental factors. Personal religiousness such as praying to God, believing in God, and finding strength and comfort in religion were more influenced by genetic factors than were social forms of religiousness such as church attendance. We found a small tendency for increasing genetic influence with increasing age for some religious items, but not for all.
The Interplay of Genes and Environment across Multiple Studies (IGEMS) group is a consortium of eight longitudinal twin studies established to explore the nature of social context effects and gene-environment interplay in late-life functioning. The resulting analysis of the combined data from over 17,500 participants aged 25–102 at baseline (including nearly 2,600 monogygotic and 4,300 dizygotic twin pairs and over 1,700 family members) aims to understand why early life adversity, and social factors such as isolation and loneliness, are associated with diverse outcomes including mortality, physical functioning (health, functional ability), and psychological functioning (well-being, cognition), particularly in later life.
Twins traditionally retain a special status in many African societies. In Guinea-Bissau, twins are often well regarded yet still suffer from a very high mortality, especially in the perinatal and infant period. At the Bandim Health Project, a health and demographic surveillance site, we have recently established one of the first twin registries in Sub-Saharan Africa. Our short-term aim is to describe twin mortality and morbidity in order to design appropriate health interventions. Our long-term goal is a large-scale database to explore the pathogenesis of prevalent diseases; for example, diabetes mellitus, metabolic syndrome, and infectious diseases such as HIV, tuberculosis, and malaria. A major focus area is also the etiology of low birth weight and how epigenetic processes might modulate the consequences of low birth weight in Sub-Saharan Africa. For this, monozygotic twin studies represent a powerful tool. Though twin studies have been carried out by the Bandim Health Project for more than 30 years, the renewed registry described here was officially established in 2009 and includes both a cohort of newborn twins and a cohort of young and adult twins. Currently more than 1,500 twins are being followed in the two cohorts combined. We believe that the registry holds exciting possibilities and will encourage the establishment of further twin registries across the region.
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.