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Biomedical subjects

Axel Skytthe

Publications and source records attributed to Axel Skytthe.

At least 19 recordsLinked to original sources
PubMed2006

Genetic influences on exercise participation in 37,051 twin pairs from seven countries.

BACKGROUND: A sedentary lifestyle remains a major threat to health in contemporary societies. To get more insight in the relative contribution of genetic and environmental influences on individual differences in exercise participation, twin samples from seven countries participating in the GenomEUtwin project were used. METHODOLOGY: Self-reported data on leisure time exercise behavior from Australia, Denmark, Finland, Norway, The Netherlands, Sweden and United Kingdom were used to create a comparable index of exercise participation in each country (60 minutes weekly at a minimum intensity of four metabolic equivalents). PRINCIPAL FINDINGS: Modest geographical variation in exercise participation was revealed in 85,198 subjects, aged 19-40 years. Modeling of monozygotic and dizygotic twin resemblance showed that genetic effects play an important role in explaining individual differences in exercise participation in each country. Shared environmental effects played no role except for Norwegian males. Heritability of exercise participation in males and females was similar and ranged from 48% to 71% (excluding Norwegian males). CONCLUSIONS: Genetic variation is important in individual exercise behavior and may involve genes influencing the acute mood effects of exercise, high exercise ability, high weight loss ability, and personality. This collaborative study suggests that attempts to find genes influencing exercise participation can pool exercise data across multiple countries and different instruments.

Adult↗
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

Low birth weight is not associated with thyroid autoimmunity: a population-based twin study.

CONTEXT: Low birth weight has been proposed as a risk factor for the development of antibodies toward thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) in adult life. However, the association could also be due to genetic or environmental factors affecting both birth weight and the development of thyroid autoantibodies. The effect of these confounders can be minimized through investigation of twin pairs. OBJECTIVE AND DESIGN: To examine the impact of low birth weight on the development of thyroid autoimmunity, we studied whether within-twin-cohort and within-twin-pair differences in birth weight are associated with differences in the serum concentration of TPOAb and TgAb in adult life. PARTICIPANTS: We studied 1024 euthyroid twin individuals who were distributed in 512 same-sex twin pairs. METHODS: Original midwife protocols were traced manually through the Provincial Archives of Denmark. TPOAb and TgAb were measured using solid-phase time-resolved fluoroimmunometric assays. RESULTS: There were no statistically significant associations between birth weight and serum concentrations of TPOAb [regression coefficient (beta) = 0.003 (95% confidence interval, -0.010 to 0.015); P = 0.67] or TgAb [beta = 0.002 (-0.010 to 0.014); P = 0.77]. When restricting the analysis to twin pairs with a within-pair difference in birth weight of 500 g or greater or to twin pairs born 4 wk or more before term, the regression coefficients were almost unchanged. Controlling for potential confounders (sex, zygosity, gestational age, TSH, and smoking) did not change the findings of nonsignificant regression coefficients. CONCLUSION: Low birth weight per se has no evident role in the etiology of thyroid autoimmunity.

Adult↗
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

Handgrip strength among nonagenarians and centenarians in three European regions.

BACKGROUND: Handgrip strength is an important predictor of disability and mortality among old people. The aim was to compare the grip strength among very old people in three regions of Europe. METHODS: In this substudy of the European Challenge for Healthy Aging project, only the long-lived probands were included. The maximum value of three measurements of handgrip strength was selected for the analysis. Adjustment for factors known to be correlated with grip strength was made by linear regression. RESULTS: Among 598 very old people (median age = 98 years) a clear North-South gradient was observed: For men, handgrip strength dropped from 24.2 kg in Southern Denmark to 20.8 kg in Languedoc-Roussillon, France and 14.2 kg in Calabria, Italy (p < .0001), whereas for women the drop was smaller (from 12.2 to 9.2 kg; p = .0021). The difference remains significant after adjustment for age, gender, housing, knee height, Activities of Daily Living (ADL) scale score, score on the Six-Item Mini-Mental State Examination, chair stand, and number of age-related diseases, although these factors explain two thirds of the variation in handgrip strength. CONCLUSIONS: Among nonagenarians and centenarians in three different European regions, we found a significant North-South gradient in handgrip strength with substantially lower values in Calabria. This finding may be due both to population background differences (e.g., genetic variations, birth weight, childhood growth) and to sociocultural differences (e.g., lifestyle, health care).

Aged↗
PubMed2006

Bio-social determinants of fertility.

This paper reviews several studies that investigated the potential role of genetic factors in determining fertility outcomes. Our review demonstrates convincingly that fertility contains genetic variance; that is, differences between humans in their genetic make-up affects their fertility outcomes and fertility-related behaviours. This finding is robust using both heritabilities and coefficients of genetic variation, and using both direct measures of fertility outcomes and also fertility precursors like fecundity, marriage, fertility expectations and attempts to get pregnant (proception). Moreover, genetic variance can change over short periods of time or across educational levels, specifically for females, and the relevance of genetic variance seems to increase during times of increasing reproductive choice.

Demography↗
PubMed2006

Twins and their health cost: consequences of multiple births on parental health and mortality in Denmark and England and Wales.

The rapid increase in twinning rates in developed countries has increased interest in the question as to whether twin mothers have higher mortality and more health problems than mothers of singletons. Here we use a national survey, the Office for National Statistics Longitudinal Study of England & Wales, and a linkage between the Danish Twin Registry and the Danish population register to examine mortality patterns after age 45 (50 for fathers) for twin parents and the whole population born from 1911 to 1950. For England and Wales, presence of limiting long-term illnesses and self-rated health status was also investigated. Overall similar health and mortality was found for twin parents and the whole population although both life table methods and survival analysis suggested a slight excess mortality among older cohorts of twin mothers in England and Wales.

Adolescent↗
PubMed2005

Twins with implanted pacemakers: Is there an increased mortality risk for the co-twin? A follow-up study based on the Danish Twin Registry and the Danish Pacemaker Register.

BACKGROUND: The main indications for implanting a cardiac pacemaker are either acquired atrio-ventricular block (AVB) or sick sinus syndrome (SSS). In general, the exact aetiology of these conditions is unknown. Genetic factors may play a role. Untreated AVB is associated with increased mortality but SSS seems to have a good prognosis. The present study was designed to assess whether first-degree relatives of these patients have an increased mortality risk. METHODS: We investigated the survival pattern of the co-twins of twins who have had a cardiac pacemaker implanted, by linking two nationwide registries in Denmark: the Danish Pacemaker Register and the Danish Twin Registry. For each "pacemaker-twin" four control-twins matched with respect to age, sex, and zygosity were selected among the twins who were alive at the time of the pacemaker implantation. A total of 159 twins with a pacemaker treated bradycardia of unknown aetiology were identified of which 73 had AVB and 64 had SSS. A total of 622 matched control-twins could be identified. The survival from age six of the co-twins of the "pacemaker-twins" was compared with that of the co-twins of the control-twins. The follow-up period ended January 1st, 2000. FINDINGS: The survival curves for the co-twins of the "pacemaker-twins" were virtually identical to those of the co-twins of the control-twins. This finding was consistent for both AVB and SSS and for monozygotic as well as dizygotic twins. CONCLUSION: No increased mortality risk could be demonstrated for first-degree relatives--including monozygotic twins--of patients with a cardiac pacemaker implanted due to either acquired AVB or SSS.

Aged↗
PubMed2005

Time trends in waiting time to pregnancy among Danish twins.

BACKGROUND: Little is known about time trends in fecundity because few population-based data are available. In a survey among female twins born from 1953 to 1976, their time to pregnancy did not differ from singletons and can be considered to represent the fecundity of the general population. METHODS: Information was collected by interview about waiting time to first pregnancy (TTP) and any periods of subfecundity among both male and female twins born between 1931 and 1952. Trends were analysed by considering the year of birth of the index person (birth cohort effect) or year at which the first attempt started (period effect). RESULTS: Eighty-five percent of male and 81.3% of female eligible twins participated. A total of 1598 male twins and 1653 female twins reported a TTP value and 1671 men and 1715 women had a value for their first attempt to conceive including unsuccessful attempts. No overall trends in either male or female TTP were observed with increasing year of birth or of starting time, after adjustment for confounders, but for attempts fecundity increased among female twins by year of birth or of starting the attempt. A decreasing risk of severe infertility with increasing year of birth or year for start of the attempt was observed among male twins, but this observation was based on only 81 men and was not seen among female twins. CONCLUSION: No decreasing trend in fecundity was observed among Danish twins born between 1931 and 1952 who had completed their reproduction. Female twins had a slight increase in fecundity, and men a decrease in severe infertility. In addition, TTP was apparently well reported and recalled for up to 50 years among both male and female twins.

Adult↗
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

A cohort study of Parkinson's disease and other neurodegenerative disorders in Danish welders.

OBJECTIVE: We sought to evaluate rates of hospitalizations for neurodegenerative disorders in a cohort of Danish metal manufacturing employees. METHODS: A retrospective cohort study was conducted from 1977 to 2002 among 27,839 male Danish metal-manufacturing employees, with 9,817 of those employed in departments engaged in mild or stainless-steel welding and 6,163 welders. RESULTS: The standardized hospitalization ratio and 95% confidence intervals (CI) for Parkinson's disease were 0.9 (CI = 0.7-1.2) for men in steel-manufacturing companies, 1.0 (CI = 0.7-1.5) for men in welding departments, and 0.9 (CI = 0.4-1.5) for welders. Observed numbers for other neurological conditions were small and not above population expectations. Analyses for time period worked, age, and duration of welding were unremarkable. CONCLUSIONS: This relatively large cohort study with long-term follow-up provides no support for the hypothesis that rates of hospitalization for Parkinson's disease or other neurological conditions are elevated under the exposure circumstances of these Danish workers.

Adult↗
PubMed2005

Risk for multiple sclerosis in dizygotic and monozygotic twins.

We investigated the risks of twins for multiple sclerosis (MS). Our data are linked registers of all Danish twins and of all Danes born between 1920 and 1970 in whom MS was diagnosed before 1997. We compared differences in the risks for MS by Cox regression and standardized incidence ratios. Our analyses suggest that dizygotic twins have an approximately 60% lower risk for MS than monozygotic twins and a 20% lower risk than singletons. Monozygotic twins appear to have a somewhat higher risk for MS than singletons albeit not statistically significant. We offer no biological explanation for our findings, but suggest that either sharing fetal life with a genotypically different individual is beneficial for the immune system or that there is a linkage between the genes that influence dizygotic twinning and other genes that protect against MS.

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↗
PubMed2004

Evidence for an association of methylene tetrahydrofolate reductase polymorphism C677T and an increased risk of fractures: results from a population-based Danish twin study.

Osteoporotic fractures are some of the major causes of morbidity and health care expenditure among the elderly. Identifying subjects at risk could be of major importance since several preventive treatments are now available. A large genetic component in the development of osteoporosis has been established. Previous studies concerning association of the common point mutation C677T in methylentetrahydrofolate reductase (MTHFR) and osteoporosis have revealed contradictory results. The aim of this study was to test the association between the MTHFR polymorphism, homocysteine, and fractures in a population-based sample of Danish twins aged 73+. In total, 689 subjects, with a mean age of 78 years, participated. Genotype and data of fractures are available from 687 subjects--144 with a previously diagnosed fracture. The genotype distribution is as follows: CC, CT, and TT genotypes, 317 (46.1%), 298 (43.3%), and 73 (10.6%), respectively. Using the proportional odds-ratio model adjusted for age, gender, and body mass Index, the odds-ratio of fracture was 1.5 per number of T alleles--meaning that fracture risk is 1.5 times higher in the CT group compared with the CC group and again 1.5 times higher in the TT group compared with the CT group. Homocysteine, smoking, and self-reported hormone use provided no significant contribution to fracture risk. Using biometrical modelling, the heritability of the liability to fractures was found to be approximately 0.10, when the effect of the MTHFR locus was included, and 0.07 when it was omitted. But both confidence intervals include zero and the estimates are therefore not significant. In conclusion, we here provide evidence for a significant impact of the MTHFR genotype on the occurrence of fractures in an elderly Danish population.

Aged↗
PubMed2004

Genetic influence on prolonged gestation: a population-based Danish twin study.

OBJECTIVE: The purpose of this study was to test a possible genetic component to prolonged gestation. STUDY DESIGN: The gestational duration of single, first pregnancies by both female and male twins was obtained by linking the Danish Twin Registry, The Danish Civil Registration System, and the Danish Medical Birth Register. A total of 2588 same-sex twin pairs of whom both cotwins became parents during 1978 to 1996 were identified. RESULTS: The concordance rate for female twin pairs for a gestation of > or =41 weeks and > or =42 weeks was higher for monozygotic twin pairs than for dizygotic twin pairs, which indicates genetic effects. Biometric modeling suggested that genetic factors account for 23% to 30% of the liability to prolonged gestation. The difference in concordance rate between monozygotic and dizygotic male twin pairs was small, and the best fitting model indicated no genetic factors. CONCLUSION: Maternal genes influence prolonged gestation. However, a substantial paternal genetic influence through the fetus was not found.

Denmark↗
PubMed2004

Is the risk of bipolar disorder in twins equal to the risk in singletons? A nationwide register-based study.

BACKGROUND: A previous study demonstrated a higher rate of schizophrenia in dizygotic twins than in the general population, and a higher rate of schizophrenia in siblings of dizygotic twins than in siblings of monozygotic twins and singletons, pointing to a common genetic predisposition for dizygotic twinning and schizophrenia. The aim of the present study was to investigate whether these findings also apply to bipolar disorder. METHODS: Through record linkage between The Danish Twin Register, The Danish Psychiatric Central Register and The Danish Civil Registration System, the rate of bipolar disorder (diagnosed for the first time during admission to hospital) in dizygotic and monozygotic twins was compared with the rate in singletons, and the rate in siblings and parents of twins was compared with the rate in siblings and parents of singletons. RESULTS: The rate of bipolar disorder was the same in dizygotic twins, monozygotic twins and singletons as well as for parents and siblings of dizygotic twins, monozygotic twins and singletons. LIMITATIONS: The study is a register-based study, only including hospitalized patients. CONCLUSION: This study shows that there is an equal rate of bipolar disorder in twins and in singletons. Assuming that DZ twinning is under some genetic influence, a differential relationship between schizophrenia and DZ twinning on one hand and bipolar disorder and DZ twinning on the other hand may suggest differences in the genetic basis of the two diseases. The finding that the rate of bipolar disorder in monozygotic twins is the same as the rate of bipolar disorder in singletons supports studies finding no association between bipolar disorder and obstetric complications.

Adult↗