The familial and genetic contribution to the association between depression and cardiovascular disease: a twin cohort study.

Depression and cardiovascular disease (ischemic heart disease and stroke) are associated in a bidirectional manner. Their relatively high heritability has led to the hypothesis that this co-occurrence is related to shared familial and genetic factors; this study aims to test this hypothesis. We included 23,498 monozygotic and 39,540 same-sex dizygotic twins from the Danish Twin Registry followed from January 1977 until December 2011 in nationwide Danish registries. We used survival analyses accounting for censoring and competing risk of death to estimate cumulative incidence, casewise concordance, relative recurrence risk, and heritability of the co-occurrence of depression and cardiovascular disease by age using monozygotic and same-sex dizygotic twin pairs. The casewise concordance of ischemic heart disease or stroke in twins whose co-twin was diagnosed with depression was at all ages similar for the monozygotic and dizygotic twin pairs and to the cumulative incidence of ischemic heart disease or stroke, respectively, in the entire twin population. A similar pattern was seen in analyses of depression risk given the co-twin being diagnosed with ischemic heart disease or stroke. Relative recurrence risk and heritability estimates were also of modest size and with confidence intervals including unity. Results were similar after stratification by gender as well as when redefining depression to include the use of antidepressant medication from 1995. Our findings do not support that co-occurrence between depression and cardiovascular disease is explainable by shared genetic factors, nor did we find strong evidence of a familial effect.

Protocol for evaluating the impact of a national school policy on physical activity levels in Danish children and adolescents: the PHASAR study - a natural experiment.

BACKGROUND: In 2014 the Danish Government introduced a wide-ranging school reform that applies to all public schools in Denmark. The reform involves changes in several aspects of the school structure and content. In a physical activity promotion perspective, a distinctive feature of the school reform is that it has become mandatory to integrate an average of 45 min of daily physical activity in the regular school day. The overarching objective of the PHASAR study is to evaluate the implementation and effect of this ambitious policy-driven physical activity promotion initiative on physical activity and overweight. This paper describes in detail the study protocol. METHODS: The evaluation is divided into a quantitative effect evaluation and a combined quantitative and qualitative process evaluation. A total of 31 schools are enrolled in the PHASAR study including more than 2,000 school-aged children. Objectively measured physical activity data are obtained in the PHASAR study in 2017/18 and compared to repeated cross sectional data collected in four historical school-based studies from 1998 to 2012. Body mass index data from 2012 to 2018 will be collected from The Child Database, which includes repeated cross-sectional assessments on approximately 100,000 children annually. In the absence of a control group, interrupted time-series analysis will be used to evaluate pre- and post-reform physical activity and body mass index levels and trends. A characterization of the school environment for physical activity promotion on a political, environmental, organizational and individual level and school implementation processes will be conducted to evaluate the implementation process. Data will be collected using interviews, surveys, document analyses and observations. DISCUSSION: The PHASAR study is a rare opportunity to evaluate the effectiveness of a nation-wide policy-driven school-based physical activity promotion initiative. The use of objectively measured pre- and post-reform physical activity and body mass index data combined with a characterization of the school implementation processes for physical activity promotion will provide a comprehensive source to evaluate the school reform. The study findings have the potential to influence national and international policy makers, health professionals and school staff.

Twin studies on cancer.

Studies on cancer loci by use of twin data reveal sources of variation in risk. The Nordic twin and cancer registries contain the largest cohort of population representative twins ever studied with more than median 40 years of follow-up. This article considers findings that show influences on familial risk and demonstrates the strengths of the matched case co-twin design for unraveling important risk factors of cancers. Studies using twin data will expectedly continue to provide insights into cancer epidemiology and genetics for the benefit of prevention and treatment.

Risk of oral clefts in twins.

BACKGROUND: Small studies have indicated that twinning increases the risk of oral cleft. METHODS: We used data from a Danish national population-based cohort study to investigate whether twinning was associated with isolated oral cleft, and to estimate the twin probandwise concordance rate and heritability. Twins (207 affected/130,710) and singletons (7766 affected/4,798,526) born from 1936 through 2004 in Denmark were ascertained by linkage among the Danish Facial Cleft Database, the Danish Twin Registry, and the Civil Registration System. We computed oral cleft prevalence and prevalence proportion ratio for twins versus singletons, stratified for 3 subphenotypes. Probandwise concordance rates and heritability for twins were estimated for 2 phenotypes--cleft lip with or without cleft palate (CL/P) and cleft palate (CP). RESULTS: The prevalence of oral cleft was 15.8 per 10,000 twins and 16.6 per 10,000 singletons (prevalence proportion ratio = 0.95; 95% confidence interval = 0.83-1.1). This prevalence was similar for monozygotic and dizygotic twins. The probandwise concordance rate was higher for CL/P for monozygotic twins than for dizygotic twins (50% vs. 8%, respectively). A similar contrast was present for CP. Recurrence risk for both types of clefts was greater in dizygotic twins than in non-twin siblings. Heritability estimates were above 90% for both CL/P and CP. CONCLUSIONS: No excess risk of oral cleft could be demonstrated for twins compared with singletons. The concordance rates and heritability estimates for both types of clefts show a strong genetic component.

Genetic influence on inflammation variables in the elderly.

BACKGROUND: Inflammation variables (C-reactive protein [CRP], fibrinogen, and soluble intercellular adhesion molecule-1 [sICAM-1]) have been identified as risk factors for cardiovascular disease. It is still not known how much the regulation of inflammatory risk factors is determined by genetic factors, and the aim of this study was to determine the heritability of these inflammation variables and of the acute phase regulating cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) at older ages. METHODS AND RESULTS: The heritability of CRP, fibrinogen, sICAM-1, IL-6, and TNF-alpha was determined in a twin study consisting of 129 monozygotic twin pairs and 153 dizygotic same-sex twins aged 73 to 94 years who participated in the Longitudinal Study of Aging of Danish Twins. Furthermore, we determined the influence of selected genetic polymorphisms on the plasma level variations. Genetic factors accounted for 20% to 55% of the variation in plasma levels of the inflammation variables. The highest heritability was found for sICAM-1. The genetic polymorphisms we studied explained only a small, insignificant part of the heritability. CONCLUSIONS: This study in elderly twins provides evidence for a substantial genetic component of inflammatory cardiovascular risk factors among the elderly.