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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.

AbstractAlthough 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.

Today, the public worries about emerging diseases and rapid changes of the frequency of well known diseases like autism, diabetes and obesity making the word epidemic part of the general discussion. Epidemiology should therefore be a basic component of medical training, yet often it is undertaught or even neglected. Concise and readable while also rigorous and thorough, An Introduction to Epidemiology for Health Professionals goes beyond standard textbook content to ground the reader in scientific methods most relevant to the current health landscape and the evolution of evidence-based medicine - valuable keys to better understanding of disease process, effective prevention, and targeted treatment. Jørn Olsen is Professor and Chair of the Department of Epidemiology at the UCLA School of Public Health.

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.

AbstractIn this work we present a new method for genetic analysis of twin data which is based on generalized estimating equations and allows for analysis of various response types (e.g., continuous, binary, counts) combined with estimation of residual correlations. The new approach allows for control of covariates of any kind (e.g., continuous, counts) by modeling the dependence of mean and variance on background variables. The proposed method was applied to identify the covariates that have a significant influence on elderly people's functional abilities, and find the estimates for the correlation coefficients of residuals for MZ and DZ twins in a sample of 2401 Danish twin 75 years of age or older. The bootstrap method was used to obtain standard errors for correlation coefficients. It was shown, that the chosen covariates have similar effects on MZ and DZ twins, and that the residual correlation in MZ twins is significantly higher than in DZ twins, which indicates that genetic factors play an etiological role in the determination of physical status of elderly people, controlled for 10 background variables.

This article investigates the fertility of Danish twins born during the periods 1870–1910 and 1953–64 in order to pursue two central questions for understanding human reproduction: Do genetic dispositions influence fertility and fertility‐related behavior? Does the relevance of the "nature versus nurture" debate shift over time or with demographic regimes? The authors find that genetic influences on fertility exist, but that their relative magnitude and pattern are contingent on gender and on the socioeconomic environment experienced by cohorts. Among females born in 1880–90 and after 1955, about 30–50 percent of the variance in fertility is due to genetic influences; these influences are substantially smaller for earlier and for interim birth cohorts. Male fertility is generally subject to smaller genetic and larger shared‐environment effects than female fertility. Because genetic effects are most prevalent in situations with deliberately controlled fertility and relatively egalitarian socioeconomic opportunities, the authors propose that the genetic dispositions affect primarily fertility behavior and motivations for having children. Analyses of fertility motivations, measured by age of first attempt to have a child, support this interpretation.

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.

Mental health is increasingly defined not only by the absence of illness but by the presence of subjective well-being (SWB). Previous cohort studies have consistently shown that indicators of SWB predict favorable life outcomes, including better mental and somatic health, and longevity. The favorable effects associated with SWB have prompted new research aimed at raising happiness and wellbeing through individual interventions and public health initiatives. Standard observational studies of individual-level associations, however, are subject to potential confounding of exposure and outcome by shared genes and environment. The present study explored the association between SWB and increased longevity, using twin pair analyses to determine whether the association is consistent with causality or is due to genetic or environmental confounding. The study sample of 3,966 twins aged 70 or older, followed for a median time period of 9 years, was drawn from the population-based Longitudinal Study of Aging Danish Twins (LSADT). The association between SWB, operationalized as affect and life satisfaction, and all-cause mortality risk was examined using between-individual and within-pair survival analyses. As expected, at the individual level, SWB predicted increased longevity. Exposure effects were also present in unadjusted and adjusted within-pair analyses of 400 dizygotic (DZ) pairs and 274 monozygotic (MZ) pairs, indicating that SWB is associated with increased longevity independent of familial factors of genes and shared environment.

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.

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.

AbstractEvidence 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.

AbstractTwinning 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.