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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.

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.

AbstractAlthough Denmark and Sweden have close cultural and historical ties, lifespans for Danes have generally been lower than those of Swedes. Recent improvements in Danish mortality after a period of stagnation have led to the suspicion that there may be positive trends at the very high ages at death within that population and that these trends could be quite different from those observed in Sweden. Although the mean ages at death for Danish and Swedish centenarians have been relatively constant at about 102 years for the cohorts born 1870–1904, the oldest-old in Denmark have been getting older, but no evidence has suggested any increase in lifespan for Swedes. Using quantile regression, we show that Danish centenarian lifespans in the 90th percentile have been lengthening, with those in 94th percentile (6 % longest-lived individuals) having a trend that is statistically significant at the 5 % level. We demonstrate that the increase observed is not due to the increasing sizes of birth cohorts and thus must be due to improving survival among this select top tier. We postulate that this super-select group in Denmark is best able to take advantage of the factors driving mortality reduction, whereas the majority of centenarians are not.

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.

AbstractWomen have consistently lower mortality rates than men at all ages and with respect to most causes. However, gender differences regarding hospital admission rates are more mixed, varying across ages and causes. A number of intuitive metrics have previously been used to explore changes in hospital admissions over time, but have not explicitly quantified the gender gap or estimated the cumulative contribution from cause-specific admission rates. Using register data for the total Danish population between 1995 and 2014, we estimated the time to first hospital admission for Danish men and women aged 60. This is an intuitive population-level metric with the same interpretive and mathematical properties as period life expectancy. Using a decomposition approach, we were able to quantify the cumulative contributions from eight causes of hospital admission to the gender gap in time to first hospital admission. Between 1995 and 2014, time to first admission increased for both, men (7.6 to 9.4 years) and women (8.3 to 10.3 years). However, the magnitude of gender differences in time to first admission remained relatively stable within this time period (0.7 years in 1995, 0.9 years in 2014). After age 60, Danish men had consistently higher rates of admission for cardiovascular conditions and neoplasms, but lower rates of admission for injuries, musculoskeletal disorders, and sex-specific causes. Although admission rates for both genders have generally declined over the last decades, the same major causes of admission accounted for the gender gap. Persistent gender differences in causes of admission are, therefore, important to consider when planning the delivery of health care in times of population ageing.