Kaare Christensen

University of Southern Denmark, Odense, South Denmark, Denmark

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Publications (540)2668.93 Total impact

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    ABSTRACT: Copy number variants (CNVs) represent a significant source of genetic variation in the human genome and have been implicated in numerous diseases and complex traits. To date, only a few studies have investigated the role of CNVs in human lifespan. To investigate the impact of CNVs on prospective mortality at the extreme end of life, where the genetic component of lifespan appears most profound, we analyzed genomewide CNV data in 603 Danish nonagenarians and centenarians (mean age 96.9 years, range 90.0-102.5 years). Replication was performed in 500 long-lived individuals from the Leiden Longevity Study (mean age 93.2 years, range 88.9-103.4 years). First, we assessed the association between the CNV burden of each individual (the number of CNVs, the average CNV length, and the total CNV length) and mortality and found a significant increase in mortality per 10 kb increase in the average CNV length, both for all CNVs (hazard ratio (HR) = 1.024, P = 0.002) and for duplications (HR = 1.011, P = 0.005), as well as per 100 kb increase in the total length of deletions (HR = 1.009, P = 0.0005). Next, we assessed the relation between specific deletions and duplications and mortality. Although no genome-wide significant associations were discovered, we identified six deletions and one duplication that showed consistent association with mortality in both or either of the sexes across both study populations. These results indicate that the genome-wide CNV burden, specifically the average CNV length and the total CNV length, associates with higher mortality in long-lived individuals.
    Aging cell 10/2015; DOI:10.1111/acel.12407 · 6.34 Impact Factor
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    ABSTRACT: Decline in cognitive abilities is a major concern in aging individuals. A potential important factor for functioning of the central nervous system in late-life stages is the KLOTHO (KL) gene. KL is expressed in various organs including the brain and is involved in multiple biological processes, for example, growth factor signaling. In the present study, 19 tagging gene variants in KL were studied in relation to 2 measures of cognitive function, a 5-item cognitive composite score and the Mini Mental State Examination, in 1,480 Danes 92-100 years of age. We found that heterozygotes for the previously reported KL-VS had poorer cognitive function than noncarriers. Two other variants positioned in the 5' end of the gene, rs398655 and rs562020, were associated with better cognitive function independently of KL-VS, and the common haplotype AG was associated with poorer cognition, consistently across two cognitive measures in two cohort strata. The haplotype effect was stronger than that of KL-VS. Two variants, rs2283368 and rs9526984, were the only variants significantly associated with cognitive decline over 7 years. We discuss an age-dependent effect of KL and the possibility that multiple gene variants in KL are important for cognitive function among the oldest old participants.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2015; DOI:10.1093/gerona/glv163 · 5.42 Impact Factor
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    ABSTRACT: Background: A longer leukocyte telomere length (LTL) in women than men has been attributed to a slow rate of LTL attrition in women, perhaps due to high estrogen exposure during the premenopausal period. Methods: To test this premise we performed a longitudinal study (an average follow-up of 12 years) in subset of the population-based Danish National Twin Registry. Participants consisted of 405 women, aged 37.5 (range 18.0 - 64.3) years, and 329 men, aged 38.8 (range 18.0 - 58.5) years, at baseline examination. Results: Women showed a longer LTL (kb ± SE) than men (baseline: 7.01 ± 0.03 vs. 6.87 ± 0.04; follow-up: 6.79 ± 0.03 vs. 6.65 ± 0.03; both p=0.005). Women displayed deceleration of LTL attrition (bp/years ± SE), as they transitioned from the premenopausal period (20.6 ± 1.0) through the perimenopausal period (16.5 ± 1.3) to the postmenopausal period (15.1 ± 1.7). Age was not associated with LTL attrition in women after statistical control for menopausal status. Men, in contrast, displayed a trend for age-dependent increase in the rate of LTL attrition, which differed significantly from the pattern in women (p for interaction=0.01). Conclusions: Results indicate that the premenopausal period is expressed in a higher rate of LTL attrition than the postmenopausal period. They further suggest that the sex gap in LTL stems from earlier ages─ the period of growth and development. The higher rate of LTL attrition in premenopausal women, we propose, might relate to estrogen-mediated increased turnover of erythrocytes, menstrual bleeding or both.
    International Journal of Epidemiology 09/2015; on line. DOI:10.1093/ije/dyv165 · 9.18 Impact Factor
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    ABSTRACT: Background: Epidemiological studies have reported that a higher perceived age is associated with poor health and higher mortality. However, the method used for the assessment of perceived age differs between studies with regard to age, gender, the number and occupation of assessors as well as the presentation of participants. Objective: It is not known whether the clinical experience of the assessor or photographic presentation have an influence on the assessment of perceived age, which the present study aimed to investigate. Methods: In a cross-sectional study of 460 women aged 25-93 years, 10 consultants and 10 residents were asked to estimate the age of each participant using three different photographic presentations: facial photograph, whole-body photograph, and combined facial and whole-body photographs. Data were analyzed by means of summary statistics and linear mixed models. Results: The inter-class correlation coefficient within each assessor group and photographic presentation varied from 0.66 to 0.75. Limits of agreement were in a broad range but were similar in the two assessor groups. The best inter-assessor agreement was obtained from photographs of both the face and the whole body. Intra- and inter-assessor agreements between photographic presentations were similar among both assessor groups. The accuracy in age assessment was significantly influenced by the photographic presentation but not by the clinical experience of the assessor. The difference in the mean perceived age of a participant of average age was estimated as +0.40 years (95% CI: -1.80; 2.59) for consultants versus residents, -2.05 years (95% CI: -2.90; -1.19) for facial photographs versus both facial and whole-body photographs, and -1.44 years (95% CI: -2.30; -0.58) for whole-body photographs versus both facial and whole-body photographs. A regression towards the mean age was seen. Conclusion: The assessment of perceived age was influenced by the photographic presentation but not by the clinical experience of the assessor.
    Gerontology 09/2015; DOI:10.1159/000438825 · 3.06 Impact Factor
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    ABSTRACT: Van der Woude syndrome (VWS) is an autosomal dominant malformation syndrome characterized by orofacial clefting (OFC) and lower lip pits. The clinical presentation of VWS is variable and can present as an isolated OFC, making it difficult to distinguish VWS cases from individuals with nonsyndromic OFCs. About 70% of causal VWS mutations occur in IRF6, a gene that is also associated with nonsyndromic OFCs. Screening for IRF6 mutations in apparently nonsyndromic cases has been performed in several modestly sized cohorts with mixed results. In the current study we screened 1521 trios with presumed nonsyndromic OFCs to determine the frequency of causal IRF6 mutations. We identified seven likely causal IRF6 mutations, although a posteriori review identified two misdiagnosed VWS families based on the presence of lip pits. We found no evidence for association between rare IRF6 polymorphisms and nonsyndromic OFCs. We combined our results with other similar studies (totaling 2,472 families) and conclude that causal IRF6 mutations are found in 0.24%-0.44% of apparently nonsyndromic OFC families. We suggest that clinical mutation screening for IRF6 be considered for certain family patterns such as families with mixed types of OFCs and/or autosomal dominant transmission.
    Clinical Genetics 09/2015; DOI:10.1111/cge.12675 · 3.93 Impact Factor
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    ABSTRACT: 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/m 2 in childhood and adolescence and up to 0.2 kg/m 2 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.
    Twin Research and Human Genetics 09/2015; DOI:10.1017/thg.2015.57 · 2.30 Impact Factor
  • European geriatric medicine 09/2015; 6:S44-S45. DOI:10.1016/S1878-7649(15)30152-2 · 0.73 Impact Factor
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    ABSTRACT: Age-related decline in grip strength predicts later life disability, frailty, lower well-being and cognitive change. While grip strength is heritable, genetic influence on change in grip strength has been relatively ignored, with non-shared environmental influence identified as the primary contributor in a single longitudinal study. The extent to which gene-environment interplay, particularly gene-environment interactions, contributes to grip trajectories has yet to be examined. We considered longitudinal grip strength measurements in seven twin studies of aging in the Interplay of Genes and Environment across Multiple Studies consortium. Growth curve parameters were estimated for same-sex pairs, aged 34-99 (N = 10,681). Fisher's test for mixture distribution of within-monozygotic twin-pair differences (N = 1724) was performed on growth curve parameters. We observed significant gene-environment interaction on grip strength trajectories. Finally, we compared the variability of within-pair differences of growth curve parameters by APOE haplotypes. Though not statistically significant, the results suggested that APOE ɛ2ɛ2/ɛ2ɛ3 haplotypes might buffer environmental influences on grip strength trajectories.
    Behavior Genetics 08/2015; DOI:10.1007/s10519-015-9736-4 · 3.21 Impact Factor
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    ABSTRACT: Increasing evidence shows that some cancers originate in utero. It is hypothesized that elevated exposure to some steroid hormones might increase cancer risk, and that hormone transfer between twin fetuses could result in different prenatal exposure to testosterone. This large-scale prospective twin study compared opposite-sex (OS) and same-sex (SS) twins to test the impact of intrauterine exposures on cancer risk. Based on the Danish and Swedish twin and cancer registries, we calculated incidence rate ratios for OS and SS twins while standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated for OS/SS twins compared with the general population. A total of 18,001 cancers were identified during 1943-2009. No significant differences were observed between OS and SS twins, neither for the sex-specific cancers nor for cancer at all sites. All-cause cancer was slightly reduced for OS and SS twins compared with the general population, significant for OS males (SIR = 0.95; 95% CI 0.92-0.98) and for SS males and females (SIR = 0.97; 95% CI 0.94-0.99). Our data suggest that having a male co-twin - which may entail higher exposure to prenatal testosterone - does not increase the risk of sex-specific cancers in OS females. Furthermore, the study supports that twinning per se is not a risk factor of cancer. Findings are reassuring as they fail to provide evidence for the hypothesis that endocrine or other difference in the in utero milieu affects the risk of sex-specific cancers. Copyright © 2015, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 08/2015; DOI:10.1158/1055-9965.EPI-15-0317 · 4.13 Impact Factor
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    ABSTRACT: It is unknown whether facial or surrounding (eg, hair and clothing) cues have the strongest influence on the perceived age of subjects in photographic images, and which drives links between perceived age and survival. In 2001, 187 Danish twin pairs (n = 374) aged 70+ years were photographed generating passport-type images. The faces of the twins in these images were swapped creating two new images per twin pair (748 images in total). Ten nurses rated the perceived age of the twin from the original and swapped facial images. The survival of the twins was determined through to the end of 2013. Changing the face or its surrounding significantly changed the perceived age of the images, with only a marginal difference between their effect sizes (difference of 0.5 years, 95% confidence interval CI -0.1 to 1.1). Perceived age, adjusting for chronological age, and sex, was a predictor of survival up to 7 years (hazard ratio 1.17, 95% CI 1.10-1.25) and also 7-12 years (hazard ratio 1.06, 95% CI 1.00-1.12) after the photographs were taken. Where the older looking twin died first they had a significantly older looking face (1.4 years older, 95% CI 0.3-2.6) but not surrounding (0.3 years older, 95% CI -0.8 to 1.4) compared to where the older looking twin died second. Facial visual cues but not hair or clothing cues drive the link between perceived age and survival. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 08/2015; DOI:10.1093/gerona/glv090 · 5.42 Impact Factor
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    ABSTRACT: To investigate whether depression symptomatology is associated with low back pain (LBP) in twins aged 70+ and whether this effect depends on a person's physical activity (PA) status. This prospective cohort and nested case-control study used a nationally representative sample of twins. Data on depression symptomatology (modified Cambridge Mental Disorders Examination) and self-reported PA were obtained from the Longitudinal Study of Aging Danish Twins using twins without LBP at baseline. Associations between depression symptomatology (highest quartile) at baseline and LBP two years later were investigated using logistic regression analyses adjusted for sex. To examine the moderating effect of PA, we tested its interaction with depression. Associations were analysed using the complete sample of 2446 twins and a matched case-control analysis of 97 twin pairs discordant for LBP at follow-up. Odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Using the whole sample, high depression scores were associated with an increased probability of LBP (OR 1.56, 95 % CI 1.22-1.99, P ≤ 0.01). There was no statistically significant interaction of light PA and depression symptomatology (OR 0.78, 95 % CI 0.46-1.35, P = 0.39) and strenuous PA and depression symptomatology (0.84, 95 % CI 0.50-1.41, P = 0.51). The case-control analysis showed similar ORs, although statistically insignificant. High depression symptomatology predicted incident LBP. This effect is supposedly not attributable to genetic or shared environmental factors. Physical activity did not moderate the effect of depression symptomatology on LBP.
    European Spine Journal 08/2015; DOI:10.1007/s00586-015-4138-0 · 2.07 Impact Factor
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    ABSTRACT: Background: Several studies in the new field of cognitive epidemiology have shown that higher intelligence predicts longer lifespan. This positive correlation might arise from socioeconomic status influencing both intelligence and health; intelligence leading to better health behaviours; and/or some shared genetic factors influencing both intelligence and health. Distinguishing among these hypotheses is crucial for medicine and public health, but can only be accomplished by studying a genetically informative sample. Methods: We analysed data from three genetically informative samples containing information on intelligence and mortality: Sample 1, 377 pairs of male veterans from the NAS-NRC US World War II Twin Registry; Sample 2, 246 pairs of twins from the Swedish Twin Registry; and Sample 3, 784 pairs of twins from the Danish Twin Registry. The age at which intelligence was measured differed between the samples. We used three methods of genetic analysis to examine the relationship between intelligence and lifespan: we calculated the proportion of the more intelligent twins who outlived their co-twin; we regressed within-twin-pair lifespan differences on within-twin-pair intelligence differences; and we used the resulting regression coefficients to model the additive genetic covariance. We conducted a meta-analysis of the regression coefficients across the three samples. Results: The combined (and all three individual samples) showed a small positive phenotypic correlation between intelligence and lifespan. In the combined sample observed r = .12 (95% confidence interval .06 to .18). The additive genetic covariance model supported a genetic relationship between intelligence and lifespan. In the combined sample the genetic contribution to the covariance was 95%; in the US study, 84%; in the Swedish study, 86%, and in the Danish study, 85%. Conclusions: The finding of common genetic effects between lifespan and intelligence has important implications for public health, and for those interested in the genetics of intelligence, lifespan or inequalities in health outcomes including lifespan.
    International Journal of Epidemiology 07/2015; DOI:10.1093/ije/dyv112 · 9.18 Impact Factor
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    ABSTRACT: A coding gene variant A673T (rs63750847) in the APP gene has recently been recognized as a protective variant of late-onset Alzheimer's Disease in a large Icelandic population and has been observed recurrently in populations from Nordic countries. The variant also was related to longevity in the Icelandic population. However, because of the extreme rarity of A673T in non-Nordic populations, the association with Alzheimer's disease has not yet been formally replicated. Because the variant has not been reported among the Danes, we aimed to study its frequency among healthy middle-age twins and oldest-old singletons and explore the possible effects on longevity and cognitive abilities. Surprisingly, only 1 of 3487 unrelated Danes carried the A673T variant, (0.014% [95% CI 0.000-0.080]), which was significantly lower than in the other Nordic countries averaging to 0.43% (95% CI 0.40-0.46). In conclusion, the A673T variant is rarer in Danes than other Nordic countries, thus precluding assessment of association with longevity or cognitive functioning. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of aging 07/2015; 36(10). DOI:10.1016/j.neurobiolaging.2015.07.011 · 5.01 Impact Factor
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    ABSTRACT: The apparent contradiction that women live longer but have worse health than men, the so called male-female health-survival paradox, is very pronounced in Russia. The present study investigates whether men in Moscow are healthier than women at the level of biomarkers, and whether the associations between biomarkers and subjective health have sex-specific patterns. Previously collected data in the study of Stress, Aging, and Health in Russia (SAHR, n = 1800) were used to examine sex differences in biomarkers and their associations with physical functioning and self-rated health. The present study found mixed directions and magnitudes for sex differences in biomarkers. Women were significantly disadvantaged with regard to obesity and waist circumference, whereas men had a tendency toward higher prevalence of electrocardiographic abnormalities. No sex differences were indicated in the prevalence of immunological biomarkers, and mixed patterns were found for lipid profiles. Many biomarkers were associated with physical functioning and general health. Obesity and waist circumference were related to lower physical functioning among females only, while major Q-wave abnormalities with high probabilities of myocardial infarction and atrial fibrillation or atrial flutter were associated with physical functioning and self-rated health among males only. No clear patterns of sex differences in prevalence of high-risk levels of biomarkers suggest that the male-female health-survival paradox is weaker at the level of health biomarkers. We found some evidence that certain biomarkers reflecting pathophysiological changes in the organism that do not possess acute health risks, but over many years may lead to physical disability, are associated with physical functioning and self-rated health in women, whereas others reflecting more serious life-threatening pathophysiological changes are associated with physical functioning and self-rated health in men.
    PLoS ONE 06/2015; 10(6):e0131691. DOI:10.1371/journal.pone.0131691 · 3.23 Impact Factor
  • Günther Deuschl · Inge Petersen · Delia Lorenz · Kaare Christensen
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    ABSTRACT: Isolated tremor in the elderly is commonly diagnosed as essential tremor (ET). The prevalence of tremor increases steeply with increasing age, whereas hereditary tremor is becoming less common. Moreover, late-manifesting tremor seems to be associated with dementia and earlier mortality. We hypothesize that different entities underlie tremor in the elderly. Two thousand four hundred forty-eight subjects from the Longitudinal Study of Aging Danish Twins older than 70 y answered screening questions for ET in 2001. Two thousan fifty-six (84%) participants drew Archimedes spirals to measure their tremor severity, and classical aging phenotypes were assessed. A subgroup of 276 individuals fulfilling either screening criteria for ET or being controls were personally assessed. Medications and mortality data are available. The spiral score increased with age. The spiral score correlated with tremor severity. For the whole cohort, mortality was significantly correlated with the spiral score, and higher spiral scores were associated with lower physical and cognitive functioning. Multivariate analysis identified higher spiral scores as an independent risk factor for mortality. In contrast, the ET patients did not show an increased but rather a lower mortality rate although it was not statistically significant. Consistent with a slower than normal aging, they were also physically and cognitively better functioning than controls. Because incident tremors beyond 70 y of age show worse aging parameters and mortality than controls and ET, we propose to label it 'aging-related tremor' (ART). This tremor starts later in life and is accompanied by subtle signs of aging both cognitively and physically. More detailed clinical features and pathogenesis warrant further assessment. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 06/2015; 30(10). DOI:10.1002/mds.26265 · 5.68 Impact Factor
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    ABSTRACT: Chromosomal telomere length shortens with repeated cell divisions. Human leukocyte DNA telomere length (LTL) has been shown to shorten during aging. LTL shortening has correlated with decreased longevity, dementia, and other age-associated processes. Because LTL varies widely between individuals in a given age group, it has been hypothesized to be a marker of biological aging. However, the principal basis for the variation of human LTL has not been established, although various studies have reported heritability. Here, we use a family-based study of longevity to study heritability of LTL in 3037 individuals. We show that LTL is shorter in older individuals, and in males, and has a high heritability (overall h(2) = 0.54). In the offspring generation, who are in middle-life, we find an ordinal relationship: persons more-closely-related to elderly probands have longer LTL than persons less-closely-related, who nonetheless have longer LTL than unrelated spouses of the offspring generation. These results support a prominent genetic underpinning of LTL. Elucidation of such genetic bases may provide avenues for intervening in the aging process. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of aging 06/2015; 36(10). DOI:10.1016/j.neurobiolaging.2015.06.017 · 5.01 Impact Factor
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    Science Advances 06/2015;
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    Science Advances 06/2015; 1(5):e1400216. DOI:10.1126/sciadv.1400216
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    ABSTRACT: 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/m 2 ) 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.
    Twin Research and Human Genetics 05/2015; 10(10):1017. DOI:10.1017/thg.2015.29 · 2.30 Impact Factor

Publication Stats

15k Citations
2,668.93 Total Impact Points


  • 1999–2015
    • University of Southern Denmark
      • Institute of Public Health
      Odense, South Denmark, Denmark
  • 1992–2014
    • Odense University Hospital
      • • Department of Clinical Biochemistry and Pharmacology
      • • Department of Endocrinology - M
      Odense, South Denmark, Denmark
    • Institut for Sygdomsforebyggelse
      København, Capital Region, Denmark
  • 2013
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 2011
    • University of Iowa
      Iowa City, Iowa, United States
  • 2003–2010
    • University of Southern Mississippi
      HBG, Mississippi, United States
  • 2007
    • The University of Warwick
      • Department of Economics
      Warwick, ENG, United Kingdom
  • 2006
    • University of Valencia
      Valenza, Valencia, Spain
  • 2005
    • Nordic Institute of Chiropractic and Clinical Biomechanics
      Odense, South Denmark, Denmark
    • Aalborg University
      Ålborg, North Denmark, Denmark
  • 1997–2005
    • Aarhus University
      • Department of Epidemiology and Social Medicine
      Aarhus, Central Jutland, Denmark
    • Aarhus University Hospital
      • Department of Clinical Epidemiology
      Aarhus, Central Jutland, Denmark
  • 2004
    • University of Minnesota Duluth
      • Department of Psychology
      Duluth, Minnesota, United States
  • 2002
    • Duke University
      Durham, North Carolina, United States
  • 1998–2002
    • Max Planck Institute for Demographic Research
      Rostock, Mecklenburg-Vorpommern, Germany
  • 2001
    • Army Center for Epidemiology and Public Health
      Marsiglia, Provence-Alpes-Côte d'Azur, France