Investigations of the subarachnoid space as a potential link between aura and headache in migraine: A case-control MRI study.

BACKGROUND: The connection between migraine aura and headache is poorly understood. Some patients experience migraine aura without headache, and patients with migraine aura with headache commonly experience milder headaches with age. The distance between the cerebral cortex and the overlying dura mater has been hypothesized to influence development of headache following aura. We tested this hypothesis by comparing approximated distances between visual cortical areas and overlying dura mater between female patients with migraine aura without headache and female patients with migraine aura with headache. METHODS: Twelve cases with migraine aura without headache and 45 age-matched controls with migraine aura with headache underwent 3.0 T MRI. We calculated average distances between the occipital lobes, between the calcarine sulci, and between the skull and visual areas V1, V2 and V3a. We also measured volumes of corticospinal fluid between the occipital lobes, between the calcarine sulci, and overlying visual areas V2 and V3a. We investigated the relationship between headache status, distances and corticospinal fluid volumes using conditional logistic regression. RESULTS: Distances between the occipital lobes, calcarine sulci and between the skull and V1, V2 and V3a did not differ between patients with migraine aura with headache and patients with migraine aura without headache. We found no differences in corticospinal fluid volumes between groups. CONCLUSION: We found no indication for a connection between visual migraine aura and headache based on cortico-cortical, cortex-to-skull distances, or corticospinal fluid volumes overlying visual cortical areas. Longitudinal studies with imaging sequences optimized for measuring the cortico-dural distance and a larger sample of patients are needed to further investigate the hypothesis.

General practitioners' assessment of interventions applied to optimize laboratory test utilization: a cross-sectional survey study.

General practitioners (GPs) in the Region of Southern Denmark were randomly allocated to a range of interventions to optimize their use of Vitamin D tests over one year. The aim of the current survey study was to investigate GPs assessment of the interventions. Using REDCap web-platform, we invited 638 GPs to participate in a survey about their experiences of guidelines, feedback reports, non-interruptive alerts, and interruptive alerts. The questions were customized for the different interventions. We received responses from only 131 GPs (21%), but no differences in gender, age, or type of GP clinic were observed between responders and invited GPs. Approximately half of the GPs found that guidelines were helpful, and a similar proportion of GPs read the feedback reports 'often' or 'always'. The pop-up alerts were accepted when used for maximum three months for often-used tests. In contrast, alerts were accepted for long periods for rarely-used tests. The groups that were exposed to the interruptive alert found it 'problematic' that it appeared every time vitamin D was requested. Guidelines and feedback reports on tests numbers were accepted, but it was previously found, that they had little effect on improving the use of biochemical tests. Pop-up alerts in the requesting IT system can produce alert fatigue. Future research should focus on developing feedback reports that - when possible - also include relevant clinical information, and pop-up alerts should for often used tests be displayed only for weeks or a few months, but can be repeated.

A randomized controlled study of biochemical tests in primary care: interventions can reduce the number of tests but usage does not become more appropriate.

OBJECTIVES: The use of laboratory tests increases worldwide, and to some extent their use is likely to be inappropriate. Although primary care is responsible for a substantial proportion of requests, this sector is less extensively investigated than hospitals. METHODS: We tested the effect of six combinations of four interventions applied to 313 primary care clinics, using vitamin D as model test (253,762 vitamin D results). We evaluated the changes in test numbers in the six intervention groups compared to the control group, and whether interventions resulted in more homogenous test use within groups or affected the distribution of test results. All interventions included information on vitamin D testing guidelines. Four groups were exposed to a non-interruptive alert in the ordering IT-system and in two groups this was supplemented by an interruptive alert. Half of the groups received monthly feedback reports. RESULTS: Application of alerts, irrespective of the combination with feedback reports, resulted in significantly reduced test numbers (maximum -46%). Guidelines either alone or combined with feedback reports did not cause significant difference from the control group. The within-group requesting pattern changed significantly for only two of the groups. The distribution of low and normal vitamin D results within groups showed no signs of more appropriate use of the test in any of the groups. CONCLUSIONS: Some of the interventions reduced the number of tests, but there were no indications of improved adherence to the guidelines. The interventions may have led to under-utilization of the test and thus should be used with care.

Increased serum SP-D in identification of high-risk smokers at high risk of COPD.

Pulmonary surfactant protein D (SP-D) is an important component of the pulmonary innate immune system with the ability to dampen cigarette smoke-induced lung inflammation. However, cigarette smoking mediates translocation of SP-D from the lung to the blood, and serum SP-D (sSP-D) has therefore previously been suggested as marker for smoke-induced lung injury. In support of this notion, associations between high sSP-D and low lung function measurements have previously been demonstrated in smokers and in chronic obstructive lung disease (COPD). The present investigations employ a 12-yr longitudinal Danish twin study to test the hypothesis that baseline sSP-D variation has the capacity to identify smokers with normal baseline lung function who are at high risk of significant future smoke-induced lung function decline. We find that sSP-D is significantly increased in those with normal lung function at baseline who develop lung function decline during follow-up compared with those who stay lung healthy. Moreover, we demonstrate that it is the smoke-induced baseline sSP-D level, and not the constitutional level, which has capacity as biomarker, and which is linearly increased with the decline in lung function during follow-up. In conclusion, we here present first observation of increased sSP-D for identification of high-risk smokers.

Gene-Environment Interplay Between Physical Exercise and Fitness and Depression Symptomatology.

Studies often report beneficial effects of physical exercise on depression symptomatology, both in clinical and community samples. In clinical samples, effects are observed using physical exercise as primary treatment and supplement to antidepressant medications and/or psychotherapies. Magnitudes vary with sample characteristics, exercise measure, and study rigor. Both propensity to exercise and vulnerability to depression show genetic influences, suggesting gene-environment interplay. We investigated this in a Danish Twin Registry-based community sample who completed a cycle fitness test and detailed assessments of depression symptomatology and regular exercise engagement that enabled estimates of typical total, intentional exercise-specific, and other metabolic equivalent (MET) expenditures. All exercise-related measures correlated negatively with depression symptomatology (- .07 to - .19). Genetic variance was lower at higher levels of cycle fitness, with genetic and shared environmental correlations of - .50 and 1.0, respectively. Nonshared environmental variance in depression was lower at higher levels of total MET, with no indications of genetic or environmental covariance. Being physically active and/or fit tended to prevent depression, apparently because fewer participants with higher levels of activity and fitness reported high depression symptomatology. This was driven by nonshared environmental influences on activity but genetic influences on physical fitness. Genetic correlation suggested people less genetically inclined toward physical fitness may also be genetically vulnerable to depression, possibly because inertia impedes activity but also possibly due to social pressures to be fit. Exercise programs for general well-being should emphasize participation, not performance level or fitness. We discuss possible interrelations between fitness aptitude and metabolism.

Migraine with visual aura associated with thicker visual cortex.

Until recent years it was believed that migraine with aura was a disorder causing intermittent neurological symptoms, with no impact on brain structure. However, recent MRI studies have reported increased cortical thickness of visual and somatosensory areas in patients with migraine with aura, suggesting that such structural alterations were either due to increased neuronal density in the areas involved, or a result of multiple episodes of cortical spreading depression as part of aura attacks. Subsequent studies have yielded conflicting results, possibly due to methodological reasons, e.g. small number of subjects. In this cross-sectional study, we recruited females aged 30-60 years from the nationwide Danish Twin Registry. Brain MRI of females with migraine with aura (patients), their co-twins, and unrelated migraine-free twins (controls) were performed at a single centre and assessed for cortical thickness in predefined cortical areas (V1, V2, V3A, MT, somatosensory cortex), blinded to headache diagnoses. The difference in cortical thickness between patients and controls adjusted for age, and other potential confounders was assessed. Comparisons of twin pairs discordant for migraine with aura were also performed. Comparisons were based on 166 patients, 30 co-twins, and 137 controls. Compared with controls, patients had a thicker cortex in areas V2 [adjusted mean difference 0.032 mm (95% confidence interval 0.003 to 0.061), V3A [adjusted mean difference 0.037 mm (95% confidence interval 0.008 to 0.067)], while differences in the remaining areas examined were not statistically significant [adjusted mean difference (95% confidence interval): V1 0.022 (-0.007 to 0.052); MT: 0.018 (-0.011 to 0.047); somatosensory cortex: 0.020 (-0.009 to 0.049)]. We found no association between the regions of interest and active migraine, or number of lifetime aura attacks. Migraine with aura discordant twin pairs (n = 30) only differed in mean thickness of V2 (0.039 mm, 95% CI 0.005 to 0.074). In conclusion, females with migraine with aura have a thicker cortex corresponding to visual areas and our results indicate this may be an inherent trait rather than a result of repeated aura attacks.

The Danish Twin Registry: An Updated Overview.

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.

Family history of systemic lupus erythematosus and risk of autoimmune disease: Nationwide Cohort Study in Denmark 1977-2013.

Objective: To provide population-based estimates of relative risk of SLE and other autoimmune diseases (ADs) in relatives of SLE patients. Methods: A cohort of 5 237 319 Danish residents identified through the Civil Registration System was coupled to their relatives through the parental link and followed for SLE and other ADs between 1977 and 2013 through linkage to the National Patient Register. Twin zygosity was established through the Danish Twin Registry. Hazard ratios (HRs) with 95% CIs were calculated using Cox proportional hazards regression analyses. Results: During 117.5 million person-years of follow-up, 3612 persons were hospitalized with SLE. HRs of SLE were high among first-degree (HR = 10.3; 95% CI: 8.25, 12.9; n = 80) and second- or third-degree relatives of SLE patients (HR = 3.60; 95% CI: 2.20, 5.90; n = 16). HRs for any AD were elevated in first-degree (HR = 1.51; 95% CI: 1.41, 1.62; n = 785) and second- or third-degree relatives of SLE patients (HR = 1.28; 95% CI: 1.18, 1.39; n = 582). Among individuals with SLE-affected first-degree relatives, the risk was significantly increased for RA (HR = 1.64; 95% CI: 1.35, 1.99; n = 103), IBD (HR = 1.21; 95% CI: 1.02, 1.43; n = 130) and type 1 diabetes mellitus (HR = 1.23; 95% CI: 1.01, 1.48; n = 106). Risk of other ADs was significantly increased both among SLE-affected first-degree (HR = 2.08; 95% CI: 1.88, 2.31; n = 371) and second- or third-degree relatives (HR = 1.38; 95% CI: 1.23, 1.54; n = 313). Conclusion: Family history of SLE is associated with a clearly elevated risk of SLE and, to a much lesser degree, of RA and other ADs.

Genetic Factors Explain Variation in the Age at Onset of Psoriasis: A Population-based Twin Study.

The aim of this study was to determine the age at onset of psoriasis in a population-based twin sample. Questionnaire-data in 10,725 twin pairs, 20-71 years of age, from the Danish Twin Registry, was collected, and analysed using survival regression analysis. Median age at onset was 25 and 28 years among women and men, respectively. The correlation between the ages was 0.84 (bootstrap standard error?=?0.044) in monozygotic twin pairs and 0.60 (0.051) in dizygotic twin pairs, permutation p?=?0.001. Age at onset of psoriasis in the index twin did not predict risk of psoriasis in the co-twin, hazard ratio (per year of later onset =?1.01 (0.99-1.03), p?=?0.434. In conclusion, these data support that the age at onset of psoriasis is, in part, an inherited property. Our results do not support that early-onset psoriasis is more genetically determined.

DCAF4, a novel gene associated with leucocyte telomere length.

BACKGROUND: Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was to establish whether DCAF4 (DDB1 and CUL4-associated factor 4) is associated with LTL. In addition, using ingenuity pathway analysis (IPA), we examined whether LTL-associated genes in the general population might partially explain the inherently longer LTL in patients with sporadic melanoma, the risk for which is increased with ultraviolet radiation (UVR). RESULTS: Genome-wide association (GWA) meta-analysis and de novo genotyping of 20 022 individuals revealed a novel association (p=6.4×10(-10)) between LTL and rs2535913, which lies within DCAF4. Notably, eQTL analysis showed that rs2535913 is associated with decline in DCAF4 expressions in both lymphoblastoid cells and sun-exposed skin (p=4.1×10(-3) and 2×10(-3), respectively). Moreover, IPA revealed that LTL-associated genes, derived from GWA meta-analysis (N=9190), are over-represented among genes engaged in melanoma pathways. Meeting increasingly stringent p value thresholds (p<0.05, <0.01, <0.005, <0.001) in the LTL-GWA meta-analysis, these genes were jointly over-represented for melanoma at p values ranging from 1.97×10(-169) to 3.42×10(-24). CONCLUSIONS: We uncovered a new locus associated with LTL in the general population. We also provided preliminary findings that suggest a link of LTL through genetic mechanisms with UVR and melanoma in the general population.

Genetic and environmental transactions underlying the association between physical fitness/physical exercise and body composition.

We examined mean effects and variance moderating effects of measures of physical activity and fitness on six measures of adiposity and their reciprocal effects in a subsample of the population-representative Danish Twin Registry. Consistent with prior studies, higher levels of physical activity suppressed variance in adiposity, but this study provided further insight. Variance suppression appeared to have both genetic and environmental pathways. Some mean effects appeared due to reciprocal influences of environmental circumstances differing among families but not between co-twins, suggesting these reciprocal effects are uniform. Some variance moderating effects also appeared due to biases in individual measures of adiposity, as well as to differences and inaccuracies in measures of physical activity. This suggests a need to avoid reliance on single measures of both physical activity and adiposity in attempting to understand the pathways involved in their linkages, and constraint in interpreting results if only single measures are available. Future research indications include identifying which physical activity-related environmental circumstances have relatively uniform effects on adiposity in everyone, and which should be individually tailored to maximize motivation to continue involvement.

The heritability of blood donation: a population-based nationwide twin study.

BACKGROUND: Voluntary blood donation is believed to be mostly motivated by altruism. Because studies have suggested that altruistic personality is determined by both genetic and environmental factors, we speculated that willingness to donate blood could also be governed by constitutional factors. This hypothesis was tested in a study among Danish twins. STUDY DESIGN AND METHODS: The nationwide Danish Twin Register, which is virtually complete for all twins born since 1968, was linked with Danish portion of the Scandinavian Donation and Transfusion (SCANDAT) Database, which includes information on all active Danish blood donors from 2002 to 2012, to establish blood donor status for Danish twins, who at age 17 years became eligible for donation in 2002 or later. Casewise concordance in monozygotic (MZ) and dizygotic (DZ) twins were presented and heritability was estimated in Mx by variance component analysis in a liability threshold model. RESULTS: A total of 274 MZ and 484 same-sex DZ twins age 17 to 27 years were identified as donors in SCANDAT. There was no difference between MZ and DZ twins with regard to age at first donation or number of donations. Casewise concordance rates were 0.61 (95% confidence interval [CI], 0.56-0.67) and 0.41 (95% CI, 0.36-0.47) in MZ and DZ twin pairs, respectively. Heritability analysis using the ACE model found that additive genetic and shared environmental effects accounted for 0.53 (95% CI, 0.33-0.73) and 0.28 (95% CI, 0.10-0.45) of the variance in the motivation to donate blood, respectively. CONCLUSION: Becoming a volunteer blood donor is determined by both genetic and environmental factors shared within families.

Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly.

The role of the mitochondria in disease, general health and aging has drawn much attention over the years. Several attempts have been made to describe how the numbers of mitochondria correlate with age, although with inconclusive results. In this study, the relative quantity of mitochondrial DNA compared to nuclear DNA, i.e. the mitochondrial DNA copy number, was measured by PCR technology and used as a proxy for the content of mitochondria copies. In 1,067 Danish twins and singletons (18-93 years of age), with the majority being elderly individuals, the estimated mean mitochondrial DNA copy number in peripheral blood cells was similar for those 18-48 years of age [mean relative mtDNA content: 61.0; 95 % CI (52.1; 69.9)], but declined by -0.54 mtDNA 95 % CI (-0.63; -0.45) every year for those older than approximately 50 years of age. However, the longitudinal, yearly decline within an individual was more than twice as steep as observed in the cross-sectional analysis [decline of mtDNA content: -1.27; 95 % CI (-1.71; -0.82)]. Subjects with low mitochondrial DNA copy number had poorer outcomes in terms of cognitive performance, physical strength, self-rated health, and higher all-cause mortality than subjects with high mitochondrial DNA copy number, also when age was controlled for. The copy number mortality association can contribute to the smaller decline in a cross-sectional sample of the population compared to the individual, longitudinal decline. This study suggests that high mitochondrial DNA copy number in blood is associated with better health and survival among elderly.

A Danish population-based twin study on autism spectrum disorders.

Genetic epidemiological studies of Autism Spectrum Disorders (ASDs) based on twin pairs ascertained from the population and thoroughly assessed to obtain a high degree of diagnostic validity are few. All twin pairs aged 3-14 years in the nationwide Danish Twin Registry were approached. A three-step procedure was used. Five items from the "Child Behaviour Checklist" (CBCL) were used in the first screening phase, while screening in the second phase included the "Social and Communication Questionnaire" and the "Autism Spectrum Screening Questionnaire". The final clinical assessment was based on "gold standard" diagnostic research procedures including diagnostic interview, observation and cognitive examination. Classification was based on DSM-IV-TR criteria. The initial sample included 7,296 same-sexed twin pairs and, after two phases of screening and clinical assessment, the final calculations were based on 36 pairs. The probandwise concordance rate for ASD was 95.2% in monozygotic (MZ) twins (n=13 pairs) and 4.3% in dizygotic (DZ) twins (n=23 pairs). The high MZ and low DZ concordance rate support a genetic aetiology to ASDs.

The use and application of Lean Management methods to research processes-a scoping review protocol.

INTRODUCTION: Waste in medical research is a relatively well-known issue. However, only a few initiatives exist to address this issue. Lean Management methods (Lean) were developed in industrial manufacturing and later applied within healthcare improvement. Overall, the results from studies of the application of Lean to healthcare appear to be positive in terms of greater efficiency regarding treatment outcomes and patient care. Nevertheless, the application of Lean to improve research processes is not well studied and, given that research alongside clinical practice and experiential knowledge provides the foundation for the treatment and care of patients, it is paramount to identify approaches and review the degree to which they increase efficiency within research procedures. Therefore, this review will scope the landscape of studies that investigated Lean and how to implement Lean in research processes, particularly regarding healthcare research. METHODS AND ANALYSIS: Our approach follows the methodological framework of Arksey and O'Malley for conducting scoping reviews (PRISMA-ScR). The search strategy for this scoping review was developed using the PCC model. We will identify the relevant literature by searching four search databases: Scopus, Web of Science, Academic Search Premier and Business Source Complete. Next, we will use citation pearl growing to identify all relevant published literature. The data charting process will follow the PRISMA-ScR checklist and will be organised using NVivo. We will generate qualitative and quantitative assessments of the extracted data by using NVivo, RStudio and Excel. We will follow the PRISMA-ScR guideline when reporting the results. ETHICS AND DISSEMINATION: The review will comprise existing published studies and no primary data will be collected. Our findings will be shared through open access peer-reviewed journals, national and international conferences and emails to all relevant collaborative relationships. We plan to disseminate our findings via academic social media platforms, newspaper articles and blogposts.

Modifications of longitudinally extensive transverse myelitis and brainstem lesions in the course of neuromyelitis optica (NMO): a population-based, descriptive study.

BACKGROUND: Neuromyelitis optica (NMO) includes transverse myelitis, optic neuritis and brain lesions. Recent studies have indicated that the brainstem is an important site of attack in NMO. Longitudinally extensive transverse myelitis (LETM) is an important component of the clinical diagnosis of NMO. The frequency of brainstem and LETM lesions, changes over time of LETM and the clinical consequences in the course of NMO have only been sparsely studied. METHODS: The study was a population-based retrospective case series with clinical and magnetic resonance imaging (MRI) follow-up of 35 patients with definite NMO and a relapsing-remitting course. RESULTS: Brainstem lesions were observed in 25 patients, 18 in medulla oblongata (11 in area postrema). Lesions in the pons, mesencephalon and diencephalon occurred in 10, 7 and 7 patients, respectively. Lesions were symptomatic in medulla oblongata and pons, asymptomatic in mesencephalon and diencephalon. Brainstem lesions were observed significantly more often in anti-aquaporin-4 (AQP-4) antibody positive than in seronegative patients (p < 0.002).LETM was demonstrated by MRI of the spinal cord in 30/36 patients, 23/30 of whom had follow-up MRI of the spinal cord. Recurrent LETM was observed in five patients. In nine patients the LETM changed into multiple lesions during remission or treatment. Spinal cord atrophy was observed in 12/23 (52%) patients, correlating to Expanded Disability Status Scale (r = 0.88, p < 0.001). CONCLUSIONS: NMO patients had frequent occurrence of brainstem lesions and LETM. Brainstem lesions were associated with anti-AQP4 antibody positivity. LETM lesions differentiated over time and the outcome included relapses, fragmentation and atrophy. Correlation was observed between spinal cord atrophy and neurological disability.

Interferon alpha association with neuromyelitis optica.

Interferon-alpha (IFN- α ) has immunoregulatory functions in autoimmune inflammatory diseases. The goal of this study was to determine occurrence and clinical consequences of IFN- α in neuromyelitis optica (NMO) patients. Thirty-six NMO and 41 multiple sclerosis (MS) patients from a population-based retrospective case series were included. Expanded Disability Status Scale (EDSS) score and MRI findings determined disease activity. Linear regression was used to assess the effects of the level of IFN- α on disability (EDSS). IFN- α was determined by sensitive ELISA assays. IFN- α was detectable in sera from 9/36 NMO patients, significantly more often than in the MS group (2/41) (P = 0.0197). A higher frequency of IFN- α was observed in NMO patients with acute relapse compared to NMO patients in remission (P < 0.001) and compared to the MS patients with relapse (P = 0.010). In NMO patients, the levels of IFN- α were significantly associated with EDSS (P = 0.0062). It may be concluded that IFN- α was detectable in a subgroup of NMO patients. Association of IFN- α levels with clinical disease activity and severity suggests a role for IFN- α in disease perpetuation and may provide a plausible explanation for a negative effect of IFN-1 treatment in NMO patients.

Heritability of health-related quality of life: SF-12 summary scores in a population-based nationwide twin cohort.

AIM: The present study aims to estimate the relative importance of genetic and environmental factors for health-related quality of life (HRQL) measured by the 12-item Short-Form Health Survey (SF-12). METHODS: The study was based on two Danish twin cohorts (46,417 twin individuals) originating from the nationwide, population-based Danish Twin Registry. The twins were approached by a mailed-out questionnaire in 2002. The questionnaire included the SF-12, information on demographic factors, and questions on a variety of specific diseases. Heritability of the SF-12 includes the physical component summary (PCS) and the mental component summary (MCS); and etiologically important variance components were estimated using multivariate biometric models. The respondents were stratified into six groups, based on age and sex. RESULTS: A total of 33,794 (73%) individual twins responded to the survey. The SF-12 was completed by 29,619 individuals, which included 9,120 complete twin pairs. Overall, the best-fitting model explaining the variance of HRQL was the ACE model. The estimated heritability of the SF-12 was between 11% and 35%, whereas between 65% and 89% could be explained by unique environmental or stochastic factors in the different sex and age groups. The highest heritability was seen among older twins. In addition, the genetic correlation between MCS and PCS scores was low (0.07 and 0.23 for males and females, respectively) among younger and high (0.26 and 0.45 for males and females, respectively) in the oldest age group. Both the largest genetic influence on HRQL and the largest genetic overlap between the scores were seen in the oldest age group, which consisted of twins older than 55. The unique environmental correlation between MCS and PCS were generally negative. CONCLUSION: The heritability of HRQL differs between different age groups. In general, most of the variance in the SF-12 summary components was determined by unique environmental factors.

The Danish Twin Registry: linking surveys, national registers, and biological information.

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.