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Kaare Christensen

Publications and source records attributed to Kaare Christensen.

At least 55 records · Page 3Linked to original sources
PubMed2005

Total and regional fat distribution is strongly influenced by genetic factors in young and elderly twins.

OBJECTIVE: Indirect estimates of obesity such as BMI seem to be strongly influenced by genetic factors in twins. Precise measurements of total and regional fat as determined by direct techniques such as DXA scan have only been applied in a few twin studies. The aim of the present study was to estimate the heritability (h(2)) of total and regional fat distribution in young and elderly Danish twins. RESEARCH METHODS AND PROCEDURES: Monozygotic (108) and dizygotic (88) twins in two age groups (25 to 32 and 58 to 66 years) underwent anthropometric measurements and DXA scans. Intraclass correlations and etiologic components of variance were estimated for total and regional fat percentages using biometric modeling. RESULTS: The intraclass correlations demonstrated higher correlations for all fat percentages among monozygotic twins as compared with dizygotic twins. The biometric modeling revealed a major genetic component (h(2)) of total (h(2)(young) = 0.83, h(2)(elderly) = 0.86) and regional fat percentages (trunk, h(2)(young) = 0.82, h(2)(elderly) = 0.85; lower body, h(2)(young) = 0.83, h(2)(elderly) = 0.81; and trunk/lower body, h(2)(young) = 0.83, h(2)(elderly) = 0.71) in both the young and elderly twins. DISCUSSION: The h(2) estimates emphasize that body fat and distribution as determined by DXA scan are under extensive genetic control.

Absorptiometry, Photon↗
PubMed2005

Twin study of genetic and aging effects on X chromosome inactivation.

To investigate the genetic influence on X chromosome inactivation and on age-related skewing of X inactivation, in particular, we analysed the X inactivation pattern (XIP) in peripheral blood cells from 118 young monozygotic (MZ) twin pairs (18-53 years), 82 elderly MZ twin pairs (55-94 years), 146 young dizygotic (DZ) twin pairs (20-54 years) and 112 elderly DZ twin pairs (64-95 years). Elderly twins had a higher frequency of skewed X inactivation (34%) than young twins (15%) (P<0.001). Our data suggest that the increase in skewing occurs after age 50-60 years. The intraclass correlation was 0.61 and 0.58 in young and elderly MZ twin pairs, and 0.08 and 0.09 in young and elderly DZ twin pairs. Biometric analysis showed that dominant genetic effects accounted for 63 and 58% of the variance of XIP in the young and elderly twin pairs, respectively. The dominant genetic effect and the shared environment for monochorionic MZ twins may explain the high intraclass correlation for the MZ twin pairs compared to the DZ twin pairs. We did not observe a significant decrease in the intraclass correlation in elderly MZ twins compared to young MZ twins, which would be expected if age-related skewing were due to stochastic factors. We conclude that the increased skewing with age implies that a genetically dependent selection of blood cells take place.

Adolescent↗
PubMed2005

No evidence for an association between extreme longevity and microsomal transfer protein polymorphisms in a longitudinal study of 1651 nonagenarians.

Previous studies have reported two SNPs and a haplotype marker within the Microsomal Transfer Protein gene associated with extreme longevity. Here, we test this finding in a longitudinal study of nonagenarians and in an association study. Participants in the Danish 1905 cohort study (1651 participants aged 92-93 years) were genotyped for the two SNPs (rs2866164 and Q95H) in the Microsomal Transfer Protein gene recently reported to be associated with longevity. The 1905 Cohort has been followed for 6.5 years, during which period 83% of the cohort has died. Furthermore, a group of 575 middle-aged Danish twins (mean age 53.7 years) were tested as a younger control group. The risk haplotype had no significant survival disadvantage (P-values: 0.56, 0.31 and 0.97 in the total population of nonagenarians, males and females, respectively) after 6.5 years of follow-up. The distributions of the suggested risk alleles (rs2866164-G and Q95) and the resulting haplotypes are very similar and not statistically different between the two age cohorts. The frequency for rs2866164-G is in the middle-aged compared to the nonagenarians 25.4 and 23.6% in males and 23.0 and 26.1% in females. The frequency for the risk haplotype is in the middle-aged compared to the nonagenarians 22.7 and 19.2% in males and 18.1 and 21.8% in females. In conclusion, our longitudinal study of survival in the 10th decade of life and an association study in a genetically homogeneous population provided no support for an association between the Microsomal Transfer Protein gene and extreme longevity.

Aged↗
PubMed2005

Characteristics of middle-aged and elderly women with urinary incontinence.

OBJECTIVE: To describe the prevalence of urinary incontinence and to find characteristics useful in general practice for identifying middle-aged and elderly women with the problem. DESIGN: Cross-sectional interview study. SETTING: Population-based samples of Danes. SUBJECTS: A total of 5795 women older than 45 years (46+ years). MAIN OUTCOME MEASURES: Prevalence of incontinence and clinical characteristics assessed by standardized interview questions. RESULTS: The overall prevalence of urinary incontinence was 20% among women less than 60 years of age and 44% among those older than 80 years. Increasing age was highly associated with both forms of incontinence (stress and urge). High body mass index (BMI), chronic lung disease, and stroke were also associated with both forms, while number of children was associated with stress incontinence only. Predictive models show that 56% of women characterized by high age (older than 80 years) and overweight (BMI higher than 30) will suffer from urinary incontinence. The low-risk group defined by these two parameters (aged 46-60 years and not overweight) still had a 19% prevalence in the last month. CONCLUSION: The prevalence of urinary incontinence increased with age. Even in the low-risk groups the problem was very common in old age. Questions about incontinence should, therefore, be asked in relevant consultations with all elderly female patients.

Age Factors↗
PubMed2005

Hair loss among elderly men: etiology and impact on perceived age.

BACKGROUND: Androgenetic alopecia is the most common type of hair loss in men, but little is known about the etiology of androgenetic alopecia in elderly men and its impact on perceived age. Here we used a population-based twin study of men aged 70+ to assess the magnitude of the genetic component affecting hair loss and to examine the association between baldness and perceived age. METHODS: In the fourth wave of The Longitudinal Study of Aging Danish Twins we obtained digital photos of the face and photos of the vertex area of 739 elderly male twins, including 148 intact twin pairs. The degree of baldness and perceived age were assessed in each twin by five and nine nurses, respectively. The heritability of balding was estimated using structural-equation analysis, and it was tested whether baldness was associated with estimations of age. RESULTS: The intrapair correlation of degree of balding was consistently higher for monozygotic than for dizygotic twin pairs regardless of the baldness categorization used, and structural-equation analysis revealed a heritability of 79% (95% confidence interval, 0.40--0.85) for the mean baldness index. The remaining variation could be attributed to non-shared environmental effects. There was only a very weak and statistically nonsignificant association between baldness and overestimation of age. CONCLUSIONS: The majority of the variation in baldness in elderly men can be explained by genetic factors, and hair quantity has little impact on perceived age in elderly men.

Aged↗
PubMed2005

The influence of social relations on mortality in later life: a study on elderly Danish twins.

PURPOSE: We examined whether the presence of a spouse and the frequency of interaction with children, relatives, and friends significantly influence the risk of dying in late life. We assessed these effects separately by gender, controlling for self-reported health. In addition, we examined whether interaction with the co-twin has a different impact on mortality for identical and fraternal twins. DESIGN AND METHODS: The data set consists of 2,147 Danish twins aged 75 years and older, who were followed prospectively from 1995 to 2001. We modeled the effect of social ties on mortality by using event history analysis. RESULTS: Survival is extended by having a spouse and close ties with friends and the co-twin. However, contact frequency with friends and the co-twin is significant, respectively, only for women and identical twins. IMPLICATIONS: Investigating social relations sheds light on the life span of individuals older than 75 years of age. We stress the importance of social relations beyond the presence of the spouse for survival even at very old ages.

Aged↗
PubMed2005

Parent's age and the risk of oral clefts.

BACKGROUND: Some malformations are clearly associated with older maternal age, but the effect of older age of the father is less certain. The aim of this study is to determine the degree to which maternal age and paternal age independently influence the risk of having a child with oral clefts. METHODS: Among the 1,489,014 live births in Denmark during 1973-1996, there were 1920 children with nonsyndromic cleft lip with or without cleft palate and 956 children with nonsyndromic cleft palate. We used logistic regression to assess the impact of parental age on the occurrence of cleft lip with or without cleft palate and cleft palate. Interaction between mother's and father's age was included in the analysis. RESULTS: Separate analyses of mother's and father's age showed that older age was associated with increased risk of both cleft lip with or without cleft palate and cleft palate only. In a joint analysis, both maternal and paternal ages were associated with the risk of cleft lip with or without cleft palate, but the contribution of each was dependent on the age of the other parent. In the analysis of cleft palate only, the effect of maternal age disappeared, leaving only paternal age as a risk factor. CONCLUSION: Both high maternal age and high paternal age were associated with cleft lip with or without cleft palate. Higher paternal age but not maternal age increased the risk of cleft palate only.

Adult↗
PubMed2005

The heritability of CHD mortality in danish twins after controlling for smoking and BMI.

Cause-specific mortality data on Danish monozygotic and dizygotic twins are used to analyze heritability estimates of susceptibility to coronary heart disease (CHD) after controlling for smoking and Body Mass Index (BMI). The sample includes 1209 like-sexed twin pairs born between 1890 and 1920, where both individuals were still alive in 1966. The participants completed a questionnaire in 1966 which included questions on smoking, height and weight. The analysis was conducted with both sexes pooled due to the relatively small number of twin pairs. Follow-up was conducted from January 1, 1966 to December 31, 1993. The correlated gammafrailty model with observed covariates was used for the genetic analysis of frailty to account for censoring and truncation in the lifetime data. During the follow-up, 1437 deaths occurred, including 435 deaths due to CHD. Proportions of variance of frailty attributable to genetic and environmental factors were analyzed using the structural equation model approach. Different standard biometric models are fitted to the data to evaluate the magnitude and nature of genetic and environmental factors on mortality. Using the best-fitting model without covariates, heritability of frailty to CHD was found to be 0.45 (0.11). This result changes only slightly to 0.55 (0.13) in a DE model after controlling for smoking and BMI. This analysis underlines the existence of a substantial genetic influence on individual frailty associated with mortality caused by CHD.

Body Mass Index↗
PubMed2005

Discordant MZ twins with cleft lip and palate: a model for identifying genes in complex traits.

Monozygotic (MZ) twins may be discordant for complex traits due to differential environmental exposure in utero, epigenetic variability in imprinting, X chromosome inactivation, or stochastic effects. Occasionally MZ twins may be discordant for chromosomal and single gene disorders due to somatic mosaicism. For complex traits, which are due to the interactive effects of multiple genes and environmental factors, the affected twin of a discordant MZ pair offers the possibility for identifying somatic mutations in candidate genes. DNA sequencing of candidate genes in discordant MZ twins can identify those rare etiologic mutational events responsible for the different phenotypes since the confounding effects of common single nucleotide polymorphisms are eliminated, as DNA sequences should be identical in MZ pairs. In this report we describe the extensive DNA sequencing of 18 candidate genes in a sample of MZ and dizygotic (DZ) twins with nonsyndromic cleft lip with or without cleft palate. We were unable to identify any somatic differences in approximately 34 Kb of DNA sequenced in 13 MZ pairs, for a total of approximately 900 Kb of sequence comparisons, supporting the hypothesis that nonetiologic posttwinning mutations are rare. While no etiologic variants were identified in this study, sequence comparisons of discordant MZ twins can serve as a tool for identifying etiologic mutations in clefting and other complex traits.

Cleft Lip↗
PubMed2005

Genetic factors in seizures: a population-based study of 47,626 US, Norwegian and Danish twin pairs.

The purpose of the study was to describe a large sample of twins reporting a history of seizures, to characterize seizures in the three subpopulations, and to estimate the relative importance of genetic and environmental factors in seizure occurrence. Seizure history was determined by questionnaires completed by twins in population-based twin registries in the United States, Norway and Denmark. Concordance rates were calculated for all seizure categories within and across twin populations. Of 47,626 twin pairs evaluated, 6234 reported a history of seizures in one or both twins. Concordance rates were significantly higher for monozygotic (MZ) versus dizygotic (DZ)pairs for all seizure categories within and across populations. The results of this study involving the largest unselected, population-based sample of twins with seizures assembled to date confirm the importance of genetic factors in determining risk for epilepsy, febrile seizures, other seizures and staring spells. This sample is likely to provide an important resource for studying the genetics of epilepsy subtypes and febrile seizures.

Adolescent↗
PubMed2005

Telomere length among the elderly and oldest-old.

Human chromosomes terminate in a number of repeats of the sequence TTAGGG. At birth, each chromosome end is equipped with approximately 15 kb of telomere sequence, but this sequence is shortened during each cell division. In cell cultures telomere shortening is associated with senescence, a phenomenon that has also been observed in normal adult tissues, indicating that telomere loss is associated with organismal ageing. Previous work has established that the rate of telomere loss in humans is age dependent, and recent work shows a sex-specific difference in telomere length and shortening in individuals over the age span of 20 to 75 years. Here, terminal restriction fragment lengths on DNA purified from whole blood were measured to examine the mean telomere length in a cross-sectional cohort of 816 Danish individuals of age 73 to 101 years. In this age group, females show a linear correlation between telomere length and age, whereas the pattern tends to be nonlinear (quadratic in age) for males. This difference in telomere length dynamics between the 2 sexes may be caused by several different mechanisms, including differences in selection by mortality, differences in leukocyte population or different telomerase expression pattern.

Aged↗
PubMed2005

The heritability of telomere length among the elderly and oldest-old.

A tight link exists between telomere length and both population doublings of a cell culture and age of a given organism. The more population doublings of the cell culture or the higher the age of the organism, the shorter the telomeres. The proposed model for telomere shortening, called the end replication problem, explains why the telomere erodes at each cellular turnover. Telomere length is regulated by a number of associated proteins through a number of different signaling pathways. The determinants of telomere length were studied using whole blood samples from 287 twin pairs aged 73 to 95 years. Structural equation models revealed that a model including additive genetic effects and non-shared environment was the best fitting model and that telomere length was moderately heritable, with an estimate that was sensitive to the telomere length standardization procedure. Sex-specific analyses showed lower heritability in males, although not statistically significant, which is in line with our earlier finding of a sex difference in telomere dynamics among the elderly and oldest-old.

Aged↗
PubMed2005

Changing lifestyles and oral clefts occurrence in Denmark.

OBJECTIVE: The aim of this project was to assess whether any changes in the birth prevalence of cleft lip with/without cleft palate (CL[P]) occurred in Denmark during the period 1988 through 2001. In this period an official recommendation of a supplementation of folic acid to pregnant women was introduced; furthermore, smoking among pregnant women decreased considerably. DESIGN AND SETTINGS: There are few places in which ecological studies of oral clefts are possible. Denmark provides a particularly good setting for this kind of study because of a high ascertainment and a centralized registration of subjects with cleft over the last 65 years. PARTICIPANTS: Cleft occurrence in Denmark from 1936 to 1987 has previously been reported. Here we extend the study to include all live-born children with oral clefts born in Denmark in 1988 through 2001. Among a total of 992,727 live births, 1332 children with CL(P) were born during this period. RESULTS AND CONCLUSIONS: The birth prevalence of CL(P) in Denmark has previously been found to be constant in the period 1962 through 1987, with a frequency of 1.4 to 1.5 per 1000 live births. This study showed a similar occurrence in 1988 through 2001 (birth prevalence = 1.44 per 1000 live births, 95% confidence interval = 1.37 to 1.52). The introduction of folic acid and the decrease in smoking prevalence among pregnant women do not seem to have reduced the birth prevalence. This may be due to noncompliance with the folic acid recommendation and/or only a weak causal association between folic acid and smoking and occurrence of CL(P).

Cleft Lip↗
PubMed2005

Heritability of insulin secretion, peripheral and hepatic insulin action, and intracellular glucose partitioning in young and old Danish twins.

The etiology of type 2 diabetes is multifactorial, including genetic as well as pre- and postnatal factors that influence several different defects of glucose homeostasis, primarily in muscle, beta-cells, and liver. In the present twin study, we report heritability estimates (h(2)) for measures of insulin secretion, insulin resistance, hepatic glucose production (HGP), and intracellular glucose partitioning using gold standard methods (euglycemic-hyperinsulinemic clamp technique, tritiated glucose infusion, indirect calorimetry, and intravenous glucose tolerance testing) among 110 younger (22-31 years of age) and 86 older (57-66 years of age) twins. To obtain a valid estimate of beta-cell function, insulin secretion was adjusted for the individual degree of insulin action (disposition index). In both age-groups there was a major genetic component in the etiology of insulin secretion that was statistically significantly higher among older twins (young h(2) = 0.75 [0.55-0.86] and old h(2) = 0.84 [0.69-0.92], P < 0.05). The heritability estimates for peripheral insulin sensitivity (young h(2) = 0.53 [0.28-0.71] and old h(2) = 0.55 [0.20-0.76]) and nonoxidative glucose metabolism (young h(2) = 0.50 [0.32-0.64] and old h(2) = 0.48 [0.04-0.72]) were similar in younger and older twins, supporting the notion of both genetic and environmental etiological factors in the control of insulin action and nonoxidative glucose metabolism. The results suggested that HGP was predominantly controlled by nongenetic factors in both young and old twins. In conclusion, we provide further evidence for a role of genes in controlling insulin secretion, insulin action, and nonoxidative glucose metabolism. The relative contribution of genes versus environment on in vivo insulin secretion exhibited an age dependency with a slightly greater relative impact of genes among older as compared with younger twins.

Adult↗
PubMed2005

Impact of genetic versus environmental factors on the control of muscle glycogen synthase activation in twins.

Storage of glucose as glycogen accounts for the largest proportion of muscle glucose metabolism during insulin infusion in normal and insulin-resistant subjects. Studies in first-degree relatives have indicated a genetic origin of the defective insulin activation of muscle glycogen synthase (GS) in type 2 diabetes. The aim of this study was to evaluate the relative impact of genetic versus nongenetic factors on muscle GS activation and regulation in young and elderly twins examined with a 2-h euglycemic-hyperinsulinemic (40 mU x m(-2) x min(-1)) clamp combined with indirect calorimetry and excision of muscle biopsies. The etiological components were determined using structural equation modeling. Fractional GS activity; GS phosphorylation at sites 2, 2 + 2a, and 3a + 3b corrected for total GS protein; and GS kinase 3 (GSK3) activity were similar in both age groups, whereas total GS activity and protein were lower in elderly compared with younger twins. GS fractional activity increased significantly during insulin stimulation in both young and elderly twins. Conversely, there was a significant decrease in GS phosphorylation at site 3a + 3b and GSK3 activity during insulin stimulation in both age groups, whereas GS phosphorylation at site 2 and 2 + 2a only decreased on insulin stimulation in the younger twins. The increment in whole-body glucose disposal (Rd) and nonoxidative glucose metabolism (insulin - basal) correlated significantly with the increment in GS fractional activity. Fractional GS activity had a major environmental component in both age groups. GSK3 activity exhibited a genetic component in young (basal: a2 = 0.42; insulin: a2 = 0.58) and elderly (insulin: a2 = 0.56) twins. Furthermore, GS phosphorylation at site 2 (insulin: a2 = 0.69) in the elderly and at site 3a + 3b (insulin: a2 = 0.50) in the young twins had a genetic component. In conclusion, GSK3 activity and GS phosphorylation, particularly at sites 2 and 3a + 3b, had major genetic components. Total and fractional GS activities per se were, on the other hand, predominantly controlled by environmental factors. Moreover, GS activity was intact with increasing age, despite a significant reduction in nonoxidative glucose metabolism.

Adult↗