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Biomedical subjects

Kaare Christensen

Publications and source records attributed to Kaare Christensen.

At least 19 recordsLinked to original sources
PubMed2024

End of Life Events and Causes of Death in Danish Long-Lived Siblings: Reduced Dementia Risk Compared to Sporadic Long-Livers.

BACKGROUND: Better physical robustness and resilience of long-lived siblings compared to sporadic long-livers has been demonstrated in several studies. However, it is unknown whether long-lived siblings also end their lives better. OBJECTIVE: To investigate end-of-life (EoL) events (dementia diagnosis, medication, hospitalizations in the last 5 years of life), causes of death, and location of death in long-lived siblings compared to matched sporadic long-livers from the Danish population. METHODS: Long-lived siblings were identified through three nationwide Danish studies in which the inclusion criteria varied, but 99.5% of the families had at least two siblings surviving to age 90 + . Those who died between 2006 and 2018 were included, and randomly matched with sex, year-of-birth and age-at-death controls (i.e., sporadic long-lived controls) from the Danish population. RESULTS: A total of 5,262 long-lived individuals were included (1,754 long-lived siblings, 3,508 controls; 63% women; median age at death 96.1). Long-lived siblings had a significantly lower risk of being diagnosed with dementia in the last years of life (p = 0.027). There was no significant difference regarding the number of prescribed drugs, hospital stays, days in hospital, and location of death. Compared to controls, long-lived siblings presented a lower risk of dying from dementia (p = 0.020) and ill-defined conditions (p = 0.030). CONCLUSIONS: In many aspects long-lived siblings end their lives similar to sporadic long-livers, with the important exception of lower dementia risk during the last 5 years of life. These results suggest that long-lived siblings are excellent candidates for identifying environmental and genetic protective factors of dementia.

Humans↗
PubMed2007

Infertility, infertility treatment and twinning: the Danish National Birth Cohort.

BACKGROUND: We have previously observed that an increasing time to pregnancy (TTP) is associated with a reduced frequency of twin deliveries in couples not receiving infertility treatment. By using updated information, we assessed the frequencies of dizygotic (DZ) and monozygotic (MZ) twin deliveries as a function of infertility (TTP > 12 months), as well as infertility treatment. METHODS: From the Danish National Birth Cohort (1997-2003), we identified 51 730 fertile couples with TTP 12 months and 5163 infertile couples who conceived after treatment. Information on zygosity, available for part of the cohort (1997-2000), was based on standardized questions on the similarities between the twins at the age of 3-5 years. RESULTS: Compared with fertile couples, the frequency of DZ twin deliveries was lower for infertile couples conceiving naturally (odds ratio 0.4, 95% confidence interval 0.2-0.7) and was much higher for infertile couples conceiving after treatment (17.3, 14.4-20.7). The frequency of DZ twin deliveries decreased with TTP in untreated couples, whereas the frequency of MZ twin deliveries remained constant. CONCLUSIONS: The frequency of DZ twin deliveries decreased with TTP and substantially increased with infertility treatment, whereas MZ twin deliveries remained substantially unchanged.

Adult↗
PubMed2007

Active lifestyle protects against incident low back pain in seniors: a population-based 2-year prospective study of 1387 Danish twins aged 70-100 years.

STUDY DESIGN: Prospective cohort study of twins. OBJECTIVES: To investigate associations between physical activity, physical function, and incident low back pain (LBP) in an elderly population. SUMMARY OF BACKGROUND DATA: The relationship between an active lifestyle and LBP in seniors is unknown. METHODS: Participants in the population-based Longitudinal Study of Aging Danish Twins free from LBP at baseline (no LBP during the past month) were included, and interview data on physical activity, overall physical function, and LBP at baseline and follow-up were obtained. Associations between levels of physical activity and LBP were estimated using logistic regression for the entire cohort, and using a matched case-control design for twin pairs discordant for physical activity. Absolute risk and relative risks for incident LBP in relation to physical activity were calculated for participants with higher or lower than average physical function at baseline. Absolute risk for LBP was also calculated for participants based on whether they remained active or inactive between baseline and follow-up or changed activity level. RESULTS: A total of 1387 persons aged 70-100 at baseline were included in the analyses, including 86 twin pairs discordant for physical activity at baseline. In the total sample, 83% were engaged in light physical activity, and 42% of men and 35% of women were engaged in strenuous physical activity at least weekly. Being engaged in strenuous physical activity at baseline was strongly protective in relation to both having had any LBP (odds ratio 0.21, 95% confidence interval 0.12-0.37 for intra-pair analysis) and having had LBP lasting more than 30 days altogether during the past year at follow-up (odds ratio 0.08, 95% confidence interval 0.03-0.18 for intra-pair analysis). Statistically significant dose-response associations between increasing frequency of strenuous physical activity and magnitude of this protective effect were found. Participants with poor initial physical function experienced the strongest protective effect of strenuous physical activity. Finally, LBP does not appear to be an important factor affecting whether participants remained engaged in strenuous physical activity at baseline and follow-up or vice versa. CONCLUSIONS: Strenuous physical activity at least once a week is protective for incident LBP in seniors.

Aged↗
PubMed2007

Genetic influences on mannan-binding lectin (MBL) and mannan-binding lectin associated serine protease-2 (MASP-2) activity.

The lectin pathway of the complement system is activated when Mannan-binding lectin (MBL) in complex with MASP-2 binds microorganisms. Polymorphisms in both genes are responsible for low serum levels, which associate with increased risk of infection and autoimmune disease. The present study includes 1215 MBL measurements and 1214 MASP-2 activity measurements in healthy Danish adult twins. Total MASP-2 activity was estimated by C4 cleaving activity of samples diluted in an excess of MBL. Twin-twin correlations were higher in monozygotic (MZ) than in dizygotic (DZ) twins for both traits. Heritabilites of MBL levels and MASP-2 activity were estimated using structural equation modeling allowing assessment of the contribution of common genes affecting both traits. The estimated heritability was 0.77 [95% CI 0.64;0.91] for MBL levels and 0.75 [95% CI 0.59;0.81] for MASP-2 activity with the presence of additive genetic factors, shared environmental factors, and non-shared environmental factors. The genetic correlation, i.e., common genetic factors affecting MBL and MASP-2 activity was estimated to r(g) = 0.34 [0.25;0.42]. The data indicate a strong genetic influence for the serum levels of MBL and for MASP-2 activity with a significant genetic correlation between the two traits.

Adult↗
PubMed2006

[Why Danes are smug--a comparative study of life satisfaction in the EU].

Danes are by far the most content citizens in the EU. We test a number of (im)plausible hypotheses and find that the solid depth of Danish well-being is multifactorial, but with two decisive factors: winning the 1992 European Championship in football and having constantly low (and undoubtedly realistic) expectations for the coming year. With an undoubtedly disappointing 2007 in store, we do not wish to foster false hopes. However, some tepid comfort might perhaps be taken from the fact that if you lower your expectations enough, you might feel a bit better next New Year.

English Abstract↗
PubMed2006

Orofacial cleft risk is increased with maternal smoking and specific detoxification-gene variants.

Maternal smoking is a recognized risk factor for orofacial clefts. Maternal or fetal pharmacogenetic variants are plausible modulators of this risk. In this work, we studied 5,427 DNA samples, including 1,244 from subjects in Denmark and Iowa with facial clefting and 4,183 from parents, siblings, or unrelated population controls. We examined 25 single-nucleotide polymorphisms in 16 genes in pathways for detoxification of components of cigarette smoke, to look for evidence of gene-environment interactions. For genes identified as related to oral clefting, we studied gene-expression profiles in fetal development in the relevant tissues and time intervals. Maternal smoking was a significant risk factor for clefting and showed dosage effects, in both the Danish and Iowan data. Suggestive effects of variants in the fetal NAT2 and CYP1A1 genes were observed in both the Iowan and the Danish participants. In an expanded case set, NAT2 continued to show significant overtransmission of an allele to the fetus, with a final P value of .00003. There was an interaction between maternal smoking and fetal inheritance of a GSTT1-null deletion, seen in both the Danish (P=.03) and Iowan (P=.002) studies, with a Fisher's combined P value of <.001, which remained significant after correction for multiple comparisons. Gene-expression analysis demonstrated expression of GSTT1 in human embryonic craniofacial tissues during the relevant developmental interval. This study benefited from two large samples, involving independent populations, that provided substantial power and a framework for future studies that could identify a susceptible population for preventive health care.

Arylamine N-Acetyltransferase↗
PubMed2006

PVRL1 variants contribute to non-syndromic cleft lip and palate in multiple populations.

Poliovirus Receptor Like-1 (PVRL1) is a member of the immunoglobulin super family that acts in the initiation and maintenance of epithelial adherens junctions and is mutated in the cleft lip and palate/ectodermal dysplasia 1 syndrome (CLPED1, OMIM #225000). In addition, a common non-sense mutation in PVRL1 was discovered more often among non-syndromic sporadic clefting cases in Northern Venezuela in a previous case-control study. The present work sought to ascertain the role of PVRL1 in the sporadic forms of orofacial clefting in multiple populations. Multiple rare and common variants from all three splice isoforms were initially ascertained by sequencing 92 Iowan and 86 Filipino cases and CEPH controls. Using a family-based analysis to examine these variants, the common glycine allele of the G361V coding variant was significantly overtransmitted among all orofacial clefting phenotypes (P = 0.005). This represented G361V genotyping from over 800 Iowan, Danish, and Filipino families. Among four rare amino acid changes found within the V1 and C1 domains, S112T and T131A were found adjacent to critical amino acid positions within the V1 variable domain, regions previously shown to mediate cell-to-cell and cell-to-virus adhesion. The T131A variant was not found in over 1,300 non-affected control samples although the alanine is found in other species. The serine of the S112T variant position is conserved across all known PVRL1 sequences. Together these data suggest that both rare and common mutations within PVRL1 make a minor contribution to disrupting the initiation and regulation of cell-to-cell adhesion and downstream morphogenesis of the embryonic face.

Alleles↗
PubMed2006

Comparison of academic performance of twins and singletons in adolescence: follow-up study.

OBJECTIVES: To determine whether twins in recent cohorts show similar academic performance in adolescence to singletons and to test the effect of birth weight on academic performance in twins and singletons. DESIGN: Follow-up study. SETTING: Denmark. PARTICIPANTS: All twins (n=3411) and a 5% random sample of singletons (n=7796) born in Denmark during 1986-8. MAIN OUTCOME MEASURES: Test scores in ninth grade (age 15 or 16), birth weight, gestational age at birth, parents' age, and parents' education. RESULTS: Ninth grade test scores were normally distributed, with almost identical mean and standard deviations for twins and singletons (8.02 v 8.02 and 1.05 v 1.06) despite the twins weighing on average 908 g (95% confidence interval 886 to 930 g) less than the singletons at birth. Controlling for birth weight, gestational age at birth, age at test, and parents' age and education confirmed the similarity of test scores for twins and singletons (difference 0.04, 95% confidence interval -0.03 to 0.10). A significant, positive association between test score and birth weight was observed in both twins and singletons, but the size of the effect was small: 0.06-0.12 standard deviations for every kilogram increase in birth weight. CONCLUSIONS: Although older cohorts of twins have been found to have lower mean IQ scores than singletons, twins in recent Danish cohorts show similar academic performance in adolescence to that of singletons. Birth weight has a minimal effect on academic performance in recent cohorts; for twins this effect is best judged relative to what is a normal birth weight for twins and not for singletons.

Adolescent↗
PubMed2006

Candidate gene polymorphisms in the serotonergic pathway: influence on depression symptomatology in an elderly population.

BACKGROUND: Depressed mood is a major concern in the elderly, with consequences for morbidity and mortality. Previous studies have demonstrated that genetic factors in depression and subsyndromal depressive symptoms are no less important in the elderly than during other life stages. Variations in genes included in the serotonin system have been suggested as risk factors for various psychiatric disorders but may also serve as candidates for normal variations in mood. METHODS: This study included 684 elderly Danish twins to investigate the influence of 11 polymorphisms in 7 serotonin system genes on the mean level of depression symptomatology assessed over several years, reflecting individuals' underlying mood level. RESULTS: A suggestive association of sequence variations in genes responsible for the synthesis (TPH), recognition (5-HTR2A), and degradation (MAOA) of serotonin with depression symptomatology was found, although the effect was generally restricted to men. We also found that a specific haplotype in VMAT2, the gene encoding the vesicular monoamine transporter, was significantly associated with depression symptoms in men (p= .007). CONCLUSIONS: These results suggest that variations in genes encoding the components of serotonin metabolism may influence the basic mood level and that different genetic factors may apply in men and women.

Affect↗
PubMed2006

Physical and mental function and incident low back pain in seniors: a population-based two-year prospective study of 1387 Danish Twins aged 70 to 100 years.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To investigate whether physical performance, grip strength, cognitive function, and depression symptomatology are risk factors for incident low back pain (LBP) over a 2-year period in seniors. SUMMARY OF BACKGROUND DATA: LBP is common in the older age groups, but little is known about predictors of LBP in this age group. METHODS: Data from the 2001 and 2003 data collection from the population-based Longitudinal Study of Aging Danish Twins formed the basis of this analysis. Participants free from LBP at baseline (no LBP during the past month, N = 1387) were included and interview data on overall physical function, and assessment of grip strength, overall cognitive function, and depression at baseline were obtained. LBP status at follow-up was assessed using a modified version of the Standardized Nordic Questionnaire. Logistic regression was used to assess the associations between the baseline risk factors and LBP at follow-up. RESULTS: A total of 1387 persons 70 to 100 years of age at baseline were included in the analyses. Of the initially LBP-free individuals, 7% had experienced LBP more than 30 days out of the past year, 7% had altered or decreased their physical activities due to LBP, and 11% had received treatment for LBP at follow-up. Good overall physical function (being among the top 50%) at baseline was protective for LBP of more than 30 days duration and for diminishing physical activities due to LBP and for care seeking due to LBP. High depression scores (being among the top 25%) were strongly associated with altering or decreasing daily activities because of LBP. Grip strength and overall cognitive performance at baseline were associated with lower incidence of LBP and decreasing activities due to LBP at follow-up; however, these associations were not statistically significant. CONCLUSION: Poor overall physical function and depression symptomatology are associated with LBP and consequences of LBP in persons 70 years of age and older.

Activities of Daily Living↗
PubMed2006

Association between height and coronary heart disease mortality: a prospective study of 35,000 twin pairs.

An inverse association between height and risk of coronary heart disease (CHD) is well demonstrated, but it is not known whether this association is because of genetic factors, socioeconomic background, or other environmental factors. Four population-based twin cohorts with register-based follow-up data on CHD mortality from Denmark (1966-1996), Finland (1975-2001), and Sweden (1963-2001 and 1972-2001) were used to investigate this question; response rates varied between 65% and 86%. Together, the cohorts included 74,704 twin individuals (35,042 complete twin pairs) with 5,943 CHD deaths during 1.99 million person-years of follow-up. Cox and conditional logistic regression models were used. Per 1-standard deviation decrease in height, height was inversely associated with CHD mortality in men (hazard ratio = 1.08, 95% confidence interval (CI): 1.04, 1.12) and in women (hazard ratio = 1.06, 95% CI: 1.01, 1.10). A twin who had died from CHD was on average shorter than the co-twin within monozygotic pairs (odds ratio = 1.27, 95% CI: 1.12, 1.44, with no sex difference), whereas a weaker association was found within dizygotic pairs in men (odds ratio = 1.01, 95% CI: 0.91, 1.13) and in women (odds ratio = 1.14, 95% CI: 1.01, 1.28). The inverse association between height and CHD mortality found within monozygotic discordant twin pairs suggests that this association is because of environmental factors that directly affect height and CHD risk.

Body Height↗
PubMed2006

Genetic influence on human lifespan and longevity.

There is an intense search for longevity genes in both animal models and humans. Human family studies have indicated that a modest amount of the overall variation in adult lifespan (approximately 20-30%) is accounted for by genetic factors. But it is not known if genetic factors become increasingly important for survival at the oldest ages. We study the genetic influence on human lifespan and how it varies with age using the almost extinct cohorts of Danish, Finnish and Swedish twins born between 1870 and 1910 comprising 20,502 individuals followed until 2003-2004. We first estimate mean lifespan of twins by lifespan of co-twin and then turn to the relative recurrence risk of surviving to a given age. Mean lifespan for male monozygotic (MZ) twins increases 0.39 [95% CI (0.28, 0.50)] years for every year his co-twin survives past age 60 years. This rate is significantly greater than the rate of 0.21 (0.11, 0.30) for dizygotic (DZ) males. Females and males have similar rates and these are negligible before age 60 for both MZ and DZ pairs. We moreover find that having a co-twin surviving to old ages substantially and significantly increases the chance of reaching the same old age and this chance is higher for MZ than for DZ twins. The relative recurrence risk of reaching age 92 is 4.8 (2.2, 7.5) for MZ males, which is significantly greater than the 1.8 (0.10, 3.4) for DZ males. The patterns for females and males are very similar, but with a shift of the female pattern with age that corresponds to the better female survival. Similar results arise when considering only those Nordic twins that survived past 75 years of age. The present large population based study shows genetic influence on human lifespan. While the estimated overall strength of genetic influence is compatible with previous studies, we find that genetic influences on lifespan are minimal prior to age 60 but increase thereafter. These findings provide a support for the search for genes affecting longevity in humans, especially at advanced ages.

Adolescent↗
PubMed2006

Influence of environmental factors on facial ageing.

BACKGROUND: A recent twin study has shown that 'looking old for one's age' is associated with increased mortality. Approximately 40% of the variation in perceived age is due to non-genetic factors. OBJECTIVE: To examine environmental factors influencing perceived age controlling for diseases. DESIGN: A twin study. SETTING: In the 2001 wave of the population-based survey--the Longitudinal Study of Aging Danish Twins--participants provided information on a wide range of exposures and health indicators. Additionally, they were asked to have a face photograph taken. SUBJECTS: A total of 1826 elderly (70+) twins who had a high-quality face photograph taken. METHODS: Ten nurses assessed the visual age of each twin from the face photograph. The mean of the nurses' age estimates for each twin was used as the twin's perceived age. Multivariate linear regression and intrapair comparison (for intact twin pairs) were used for analyses. RESULTS: Statistically significant determinants of facial ageing associated with high perceived age for men were smoking (P = 0.01), sun exposure (P = 0.02) and low body mass index (BMI) (P<0.005), while for women they were low BMI (P = 0.05) and low social class (P<0.005). The number of children (men) and marital status (P = 0.08) and depression symptomatology score (women) were borderline significantly associated with facial ageing. CONCLUSION: Our study confirms previous findings of a negative influence of sun exposure, smoking and a low BMI on facial ageing. Furthermore, our study indicates that high social status, low depression score and being married are associated with a younger look, but the strength of the associations varies between genders.

Adult↗
PubMed2006

Age trajectories of grip strength: cross-sectional and longitudinal data among 8,342 Danes aged 46 to 102.

PURPOSE: The purpose is to study the age trajectory of hand-grip strength after the age of 45 years. METHODS: In this study, we use data from three large nationwide population-based surveys of Danes aged 45 to 102 years with a total of 8342 participants with grip-strength measurements and up to 4 years of follow-up. Grip strength was measured by using a portable hand dynamometer. RESULTS: Grip strength declines throughout life for both males and females, but among the oldest women, the longitudinal curve reaches a horizontal plateau. The course of the decline is estimated by using full information in the longitudinal data and is found to be almost linear in the age span of 50 to 85 years. In this age span, mean annual grip-strength loss is estimated to be 0.59 (0.02) (SE) kg for men and 0.31 (0.01) kg for women. CONCLUSION: This study confirms the previously reported grip-strength decline with increasing age. Estimates were obtained by using full-information methods from large population-representative studies. Equations of expected grip strength, as well as tables with sex-, age-, and height-stratified reference data, provide an opportunity to include grip-strength measurement in clinical care in similar populations.

Aged↗
PubMed2006

The quest for genetic determinants of human longevity: challenges and insights.

Twin studies show that genetic differences account for about a quarter of the variance in adult human lifespan. Common polymorphisms that have a modest effect on lifespan have been identified in one gene, APOE, providing hope that other genetic determinants can be uncovered. However, although variants with substantial beneficial effects have been proposed to exist and several candidates have been put forward, their effects have yet to be confirmed. Human studies of longevity face numerous theoretical and logistical challenges, as the determinants of lifespan are extraordinarily complex. However, large-scale linkage studies of long-lived families, longitudinal candidate-gene association studies and the development of analytical methods provide the potential for future progress.

Alleles↗
PubMed2006

Smoking habits, nicotine use, and congenital malformations.

OBJECTIVE: We examined whether maternal smoking and use of nicotine substitutes during the first 12 weeks of pregnancy increased the prevalence of congenital malformations in general and of certain congenital malformations in particular. METHODS: In the Danish National Birth Cohort (1997-2003) we identified 76,768 pregnancies (and their subsequent singleton births); 20,603 were exposed to tobacco smoking during the first 12 weeks of pregnancy. Birth outcomes were collected by linkage to the Central Population Register, the National Patients Register, and the National Birth Register. We identified congenital malformations from the Hospital Medical Birth Registry as they were recorded at birth or in the first year of follow-up. RESULTS: Smoking mothers were younger, weighed less, consumed more alcohol, and had received less education. Children exposed to prenatal tobacco smoking had no increase in congenital malformations prevalence compared with the nonexposed children in both crude and adjusted analyses. Children born to nonsmokers, but who used nicotine substitutes, had a slightly increased relative congenital malformations prevalence ratio; relative prevalence rate ratio was 1.61 (95% confidence interval 1.01-2.58), which represents a 60% increased risk. When the analysis was restricted to musculoskeletal malformations, the relative prevalence rate ratio was 2.63 (95% confidence interval 1.53-4.52). CONCLUSION: Our results showed no increase in congenital malformations related to prenatal tobacco smoking. However, we identified an increase of malformations risk in nonsmokers using nicotine substitutes. This finding needs to be replicated in other data sources. LEVEL OF EVIDENCE: II-2.

Adult↗
PubMed2006

No association between telomere length and survival among the elderly and oldest old.

BACKGROUND: The consistent findings of a negative correlation between telomere length and replicative potential of cultured cells, as well as a decreasing telomere length in a number of different tissues in humans with age, have led to the suggestion that telomeres play a role in cellular aging in vivo and ultimately even in organismal aging. Furthermore, one small longitudinal study of elderly individuals has suggested that longer telomeres are associated with better survival. METHODS: Telomere length was measured as mean terminal restriction fragment length on blood cells from 812 persons, age 73 to 101 years, who participated in population-based surveys in 1997-1998. Among the participants were 652 twins. The participants were followed up through the Danish Civil Registration system until January 2005, at which time 412 (51%) were dead. RESULTS: Univariate Cox regression analyses revealed that longer telomeres were associated with better survival (hazard ratios = 0.89 [95% confidence interval = 0.76-1.04] per 1 kb in males and 0.79 [0.72-0.88] per 1 kb in females, respectively). However, including age in the analyses changed the estimates to 0.97 (0.83-1.14) and 0.93 (0.85-1.03), respectively. Intrapair comparison showed that among 175 twin pairs in which at least one died during follow up, it was the twin with the shorter telomere length who died first in 97 (55%) of the pairs (95% confidence interval = 48-63%). We could not confirm the recently reported negative correlation between telomere length and obesity or between telomere length and smoking. CONCLUSION: This longitudinal study of the elderly and oldest old does not support the hypothesis that telomere length is a predictor for remaining lifespan once age is controlled for.

Aged↗