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Importance: Despite a remarkable co-occurrence of obsessive-compulsive disorder (OCD) and schizophrenia, little is known about the clinical and etiological relationship of these 2 disorders. Exploring the degree to which these disorders share etiological factors might provide useful implications for clinicians, researchers, and those with the disorders., Objectives: To assess whether patients with OCD experience an enhanced risk of developing schizophrenia and schizophrenia spectrum disorders and to determine whether a family history of OCD constitutes a risk factor for schizophrenia and schizophrenia spectrum disorders., Design, Setting, and Participants: Using individual data from longitudinal nationwide Danish registers, we conducted a prospective cohort study with 45 million person-years of follow-up. All survival analyses were adjusted for sex, age, calendar year, parental age, and place of residence at the time of birth. A total of 3 million people born between January 1, 1955, and November 30, 2006, were followed up from January 1, 1995, through December 31, 2012. During this period, 30 556 people developed schizophrenia or schizophrenia spectrum disorders., Main Outcomes and Measures: The presence of a prior diagnosis of OCD and the risk of a first lifetime diagnosis of schizophrenia and a schizophrenia spectrum disorder assigned by a psychiatrist in a hospital, outpatient clinic, or emergency department setting. Incidence rate ratios (IRRs) and accompanying 95% confidence intervals are used as measures of relative risk., Results: The presence of prior diagnosis of OCD was associated with an increased risk of developing schizophrenia (IRR = 6.90; 95% CI, 6.25-7.60) and schizophrenia spectrum disorders (IRR = 5.77; 95% CI, 5.33-6.22) later in life. Similarly, offspring of parents diagnosed as having OCD had an increased risk of schizophrenia (IRR = 4.31; 95% CI, 2.72-6.43) and schizophrenia spectrum disorders (IRR = 3.10; 95% CI, 2.17-4.27). The results remained significant after adjusting for family history of psychiatric disorders and the patient's psychiatric history., Conclusions and Relevance: A diagnosis of OCD was associated with higher rates of schizophrenia and schizophrenia spectrum disorders. The observed increase in risk suggests that OCD, schizophrenia, and schizophrenia spectrum disorders probably lay on a common etiological pathway.

Background: Pre- and perinatal factors and preschool body size may help identify children developing overweight, but these factors might have changed during the development of the obesity epidemic., Objective: We aimed to assess the associations between early life risk indicators and overweight at the age of 9 and 15 years at different stages of the obesity epidemic., Methods: We used two population-based Northern Finland Birth Cohorts including 4111 children born in 1966 (NFBC1966) and 5414 children born in 1985-1986 (NFBC1986). In both cohorts, we used the same a priori defined prenatal factors, maternal body mass index (BMI), birth weight, infant weight (age 5 months and 1 year), and preschool BMI (age 2-5 years). We used internal references in early childhood to define percentiles of body size (<50, 50-75, 75-90 and >90) and generalized linear models to study the association with overweight, according to the International Obesity Taskforce (IOTF) definitions, at the ages of 9 and 15 years., Results: The prevalence of overweight at the age of 15 was 9% for children born in 1966 and 16% for children born in 1986. However, medians of infant weight and preschool BMI changed little between the cohorts, and we found similar associations between maternal BMI, infant weight, preschool BMI, and later overweight in the two cohorts. At 5 years, children above the 90th percentile had approximately a 12 times higher risk of being overweight at the age of 15 years compared to children below the 50th percentile in both cohorts., Conclusions: The associations between early body size and adolescent overweight showed remarkable stability, despite the increase in prevalence of overweight over the 20 years between the cohorts. Using consequently defined internal percentiles may be a valuable tool in clinical practice.

Background: If preschool measures of body size routinely collected at preventive health examinations are associated with adult central obesity and metabolic syndrome, a focused use of these data for the identification of high risk children is possible. The aim of this study was to test the associations between preschool weight and body mass index (BMI) and adult BMI, central obesity and metabolic alterations., Methods: The Northern Finland Birth Cohort 1966 (NFBC1966) (N = 4111) is a population-based cohort. Preschool weight (age 5 months and 1 year) and BMI (age 2-5 years) were studied in relation to metabolic syndrome as well as BMI, waist circumference, lipoproteins, blood pressure, and fasting glucose at the age of 31 years. Linear regression models and generalized linear regression models with log link were used., Results: Throughout preschool ages, weight and BMI were significantly linearly associated with adult BMI and waist circumference. Preschool BMI was inversely associated with high-density lipoprotein levels from the age of 3 years. Compared with children in the lower half of the BMI range, the group of children with the 5% highest BMI at the age of 5 years had a relative risk of adult obesity of 6.2(95% CI:4.2-9.3), of adult central obesity of 2.4(95% CI:2.0-2.9), and of early onset adult metabolic syndrome of 2.5(95% CI:1.7-3.8)., Conclusions: High preschool BMI is consistently associated with adult obesity, central obesity and early onset metabolic syndrome. Routinely collected measures of body size in preschool ages can help to identify children in need of focused prevention due to their increased risk of adverse metabolic alterations in adulthood.

Importance: There has been recent interest in the findings that the offspring of older fathers have an increased risk of both de novo mutations and neuropsychiatric disorders. However, the offspring of younger parents are also at risk for some adverse mental health outcomes., Objective: To determine the association between maternal and paternal age and a comprehensive range of mental health disorders., Design, Setting, and Participants: A comprehensive, population-based record linkage study using the Danish Psychiatric Central Research Register from January 1, 1995, through December 31, 2011. A total of 2 894 688 persons born in Denmark from January 1, 1955, through December 31, 2006, were followed up during the study period., Exposures: Maternal and paternal age at the time of offspring's birth., Main Outcomes and Measures: We examined a broad range of International Classification of Diseases-defined mental disorders, including substance use; schizophrenia and related disorders; mood disorders; neurotic, stress-related, and somatoform disorders; eating disorders; specific personality disorders; and a range of developmental and childhood disorders. The incidence rate ratios for each mental disorder outcome were estimated by log linear Poisson regression with adjustments for the calendar period, age, sex, and age of the other parent., Results: The cohort was observed for 42.7 million person-years, during which 218 441 members of the cohort had their first psychiatric contact for any psychiatric disorder. Based on the overall risk of psychiatric disorders, the offspring of younger and older parents were at increased risk compared with those of parents aged 25 to 29 years. When the offspring were examined for particular disorders, the nature of the relationship changed. For example, the offspring of older fathers were at an increased risk of schizophrenia and related disorders, mental retardation, and autism spectrum disorders. In contrast, the offspring of young mothers (and to a lesser extent young fathers) were at an increased risk for substance use disorders, hyperkinetic disorders, and mental retardation., Conclusions and Relevance: The offspring of younger mothers and older fathers are at risk for different mental health disorders. These differences can provide clues to the complex risk architecture underpinning the association between parental age and the mental health of offspring.

Objectives: Genetic factors have been found to influence the risk of suicide. It is less clear if this also applies to attempted suicide. We have investigated genetic and familial environmental factors by studying the occurrence of suicide attempts in biological and adoptive siblings of adoptees who attempted suicide compared to siblings of adoptees with no suicide attempts., Method: We used a random sample of 1933 adoptees from the Danish Adoption Register, a register of non-familial adoptions of Danish children, i.e. the adoptive parents are biologically unrelated to the adoptee. Analyses were conducted on incidence rates of attempted suicide in biological and adoptive siblings given occurrence of attempted suicide in the adoptees while also taking into account psychiatric disorders. Information about suicidal attempt and history of psychiatric disorder was based on hospital admissions., Results: The rate of attempted suicide in full siblings of adoptees who attempted suicide before age 60 years was higher than in full siblings of adoptees who had not attempted suicide (incidence rate ratios (IRR)=3.45; 95% confidence interval [CI]=0.94-12.7). After adjustment for history of psychiatric admission of siblings the increased rate was statistically significant (IRR=3.88; 95% CI-1.42-10.6)., Limitations: Information on attempted suicide and psychiatric history was limited to that which involved hospitalisation., Conclusions: Genetic factors influence risk of suicide attempts., (© 2013 Published by Elsevier B.V.)

Objectives: Depression is associated with work absenteeism, reduced productivity, and significant personal and societal economic burden. We describe patterns and determinants of sick leave among working Danish antidepressant users., Methods: Persons starting antidepressant treatment (January 1, 2004 through December 31, 2005) were identified from a representative 25% sample of the Danish population by linking Danish national registries. Inclusion criteria were age 18-64 years, being in the workforce the week prior to the first antidepressant prescription (index prescription, IP), and no antidepressant prescription in the year prior to the IP. Only sick leaves >2 weeks are centrally registered in Denmark and could be assessed. Cox regression analyses identified predictors of sick leave during the year following the IP, based on previous history of sick leave and clinical and socio-demographic baseline characteristics., Results: In the cohort of 25,908 (59.7% women), sick leave prevalence increased from 37.5% (year prior to IP) to 45.3% (year after the IP); 30.7% were on sick leave for >8 weeks. Incidence peaked (35.5% of individuals) the week after the IP. Of persons with sick leave in the year before the IP, 62.7% were on sick leave the first week after the IP, vs 5.7% of those without previous sick leave. Predictors associated with increased risk of sick leave among those without previous sick leave were unemployment, female gender, age 25-54 years, couples with children, and vocational and higher intermediate education (including e.g. teachers and nurses)., Limitations: Reasons for sick leave, sick leaves of less than 14 days and the indications for antidepressant treatment were unknown., Conclusions: Sick leave was prevalent in persons starting new antidepressant use, often lasting >8 weeks. Previous sick leave was the strongest predictor of subsequent sick leave., (© 2013 Elsevier B.V. All rights reserved.)

Background: While there is clear evidence of familial influences on suicide, the origin of these is less certain. We have investigated genetic and familial environmental factors by studying the occurrence of suicide in biological and adoptive siblings of adoptees who died by suicide compared to siblings of surviving adoptees., Method: We used the Danish Adoption Register and Danish population registers to compare 221 siblings of adoptees who died by suicide with the siblings of 1,903 adoptees who did not die by suicide. All adoptions in the Danish Adoption Register are non-familial, i.e. the adoptive parents are biologically unrelated to the adoptee. Analyses were conducted on incidence rates of suicide in biological and adoptive siblings given occurrence of suicide in the adoptees while also taking into account psychiatric disorders., Results: The risk of suicide in full siblings of adoptees who died by suicide before age 60 years was significantly higher than in full siblings of adoptees who had not died by suicide (incidence rate ratios (IRR) = 5.01; 95% confidence interval [CI] = 1.28-19.6). This increase persisted after adjustment for history of psychiatric admission of siblings (IRR = 4.19; 95% CI = 1.00-17.5)., Conclusions: Genetic factors influence risk of suicide, probably independently of psychiatric disorder. This is relevant in provision of advice to families, including possible prevention of suicide.

Objectives: Offspring of older men have impaired cognitive ability as children, but it is unclear if this impairment persists into adulthood. The main objective of this study was to explore the association between paternal age at offspring birth and general cognitive ability as young adults., Design: Population-based cross-sectional study with prospectively collected data on obstetric factors and parental education., Setting: Nationwide Danish sample., Participants: Male conscripts (n = 169,009)., Primary and Secondary Outcome Measures: General cognitive ability as assessed by the Børge Priens test score, an intelligence test with components related to logical, verbal, numerical and spatial reasoning., Results: We observed an inverse U-shaped association between paternal age and general cognitive ability (slightly lower test scores in the offspring of fathers aged less than 25 years and older than 40 years, compared with fathers aged 25 to 29 years). However, after adjustment for maternal age, parental education and birth order the shape of the association changed. Offspring of fathers younger than 20 still showed slightly lower cognitive ability (-1.11 (95% CI -1.68 to -0.54)), but no significant impairments were identified in the men whose fathers were older than 29 years at the time of their birth (e.g. the mean difference in test score in the offspring of fathers aged 40 to 44 years were -0.03 [95% CI (-0.27 to 0.20)] compared with fathers aged 25 to 29 years)., Conclusions: We did not find that the offspring of older fathers had impaired cognitive ability as young adults. Whereas, we found a tendency that the offspring of teen fathers have lower cognitive ability. Thus, our results suggest that any potentially deleterious effects of older fathers on general cognitive ability as young adults may be counter-balanced by other potentially beneficial factors.

Introduction: The genetic and familial environmental influences making up familial correlations in traits and familial aggregation of diseases may be disentangled by adoption studies. Thus, resemblance between the adoptee and the biological relatives indicates a contribution of the segregating gene they have in common, and resemblance between the adoptee and the rearing adoptive family members indicates influences of the shared family environment. The Danish Adoption Register includes information on all 14,425 non-familial adoptions of Danish children legally granted in Denmark from 1924 to 1947., Research Topics: To illustrate the adoption study approach in research, we present results achieved in schizophrenia, body fatness, smoking, and mortality. Significantly higher prevalence of schizophrenia and related conditions were found in biological relatives to adoptees with schizophrenia than among biological relatives to adoptees without schizophrenia. Clear trends in body mass index of biological relatives and the weight of adoptees were found in several settings. A genetic influence on smoking habits were found within a generation. A moderate genetic influence on the mortality rate has been found., Conclusion: The Danish Adoption Register has contributed to the knowledge about environmental and genetic influence in various fields. Genetic influence on the risk of schizophrenia, body fatness, smoking habits, and on the mortality rate has been found.

Introduction: The Danish Adoption Register was established in 1963-1964 to explore the genetic and environmental contribution to familial aggregation of schizophrenia., Content: The register encompass information on all 14,425 non-familial adoptions of Danish children legally granted in Denmark 1924-1947. It includes name and date of birth of each adoptee and his or her biological and adoptive parents, date of transfer to adoptive parents and date of formal adoption., Validity and Coverage: The linkage to biological and adoptive parents is close to complete, even biological fathers are registered for 91.4% of the adoptees., Conclusion: Adoption registers are a unique source allowing disentangling of genetic and familial environmental influences on traits, risk of diseases, and mortality.

Objective: Greater paternal age is associated with increased risk of schizophrenia, and it has been hypothesized that de novo mutations in paternal germ cells are responsible for this association. An alternative hypothesis is that selection into late fatherhood accompanies a predisposition to schizophrenia. However, direct evidence of either hypothesis is lacking. If de novo mutations are responsible, greater paternal age at conception should increase the risk of schizophrenia. Conversely, if selection into late fatherhood is responsible for the association, greater age at which the father had his first child should increase the risk of schizophrenia. The authors aimed to distinguish between these two measures of paternal age., Method: A total of 2.2 million people born in Denmark between 1955 and 1992 were followed up until first diagnosis with schizophrenia. Incidence rate ratios were estimated in a Cox regression., Results: Among second- or later-born children, greater paternal age increased the risk of schizophrenia. However, when paternal age at the time of the father's first child was accounted for, the risk of schizophrenia did not depend on paternal age at the birth of later children. In contrast, the risk of schizophrenia increased significantly with increasing paternal age at the time of the father's first child., Conclusions: Factors related to greater paternal age when the father's first child was born, and not the father's age at conception of later children, are responsible for the association between paternal age and the risk of schizophrenia. These findings do not support the de novo mutation hypothesis.

Background and Objective: Adoption studies have been used to disentangle the influence of genes from shared familial environment on various traits and disease risks. However, both the factors leading to adoption and living as an adoptee may bias the studies with regard to the relative influence of genes and environment compared to the general population. The aim was to investigate whether the cohort of domestic adoptees used for these studies in Denmark is similar to the general population with respect to all-cause mortality and cause-specific mortality rates., Methods: 13,111 adoptees born in Denmark in 1917, or later, and adopted in 1924 to 1947 were compared to all Danes from the same birth cohorts using standardized mortality ratios (SMR). The 12,729 adoptees alive in 1970 were similarly compared to all Danes using SMR as well as cause-specific SMR., Results: The excess in all-cause mortality before age 65 years in adoptees was estimated to be 1.30 (95% CI 1.26-1.35). Significant excess mortality before age 65 years was also observed for infections, vascular deaths, cancer, alcohol-related deaths and suicide. Analyses including deaths after age 65 generally showed slightly less excess in mortality, but the excess was significant for all-cause mortality, cancer, alcohol-related deaths and suicides., Conclusion: Adoptees have an increased all-cause mortality compared to the general population. All major specific causes of death contributed, and the highest excess is seen for alcohol-related deaths.

Both obesity and insulin resistance have been related to low fat oxidation rates, which may be genetically determined. The association between variation in fat oxidation rates among obese subjects and genotype was studied for 42 common single-nucleotide polymorphisms (SNPs) in 26 candidate genes for fat oxidation, insulin resistance, and obesity, including FTO. Energy expenditure (EE) and fat oxidation were measured with indirect calorimetry during fasting and 3 h after a high fat load containing 95 energy% of fat (60% saturated fat, energy content 50% of estimated resting EE) in 722 obese subjects (541 women, 181 men) from 8 European centers. After adjustment for center and gender, -178 A>C CD36 (rs2232169) (P = 0.02), -22510 C>G SLC6A14 (women, rs2011162) (P = 0.03), and T690S C>G PCSK1 (rs6235) (P = 0.02) were related to a reduced fat oxidation, whereas 17 C>G SREBF1 (17 C>G) (P = 0.01) was related to increased fat oxidation in the fasting state. The ability to increase fat oxidation after a high fat load was increased in subjects with -174 G>C IL6 (rs1800795) (P = 0.01). Effect sizes range from 1.1 to 3.1% differences in fat oxidation (expressed as % of EE). FTO rs9939609 was not related to fat oxidation. At the same time, the results are not adjusted for multiple testing, thus none of the associations can be considered statistically significant. The results should therefore only be considered as leads to new hypotheses about effects of specific genetic polymorphisms on fasting and postprandial fat oxidation.

Background: Family, twin and adoption studies suggest that genetic susceptibility contributes to familial aggregation of infectious diseases or to death from infections. We estimated genetic and shared environmental influences separately on the risk of acquiring an infection (incidence) and on dying from it (case fatality)., Methods: Genetic influences were estimated by the association between rates of hospitalization for infections and between case-fatality rates of adoptees and their biological full- and half- siblings. Familial environmental influences were investigated in adoptees and their adoptive siblings. Among 14,425 non-familial adoptions, granted in Denmark during the period 1924-47, we selected 1,603 adoptees, who had been hospitalized for infections and/or died with infection between 1977 and 1993. Their siblings were considered predisposed to infection, and compared with non-predisposed siblings of randomly selected 1,348 adoptees alive in 1993 and not hospitalized for infections in the observation period. The risk ratios presented were based on a Cox regression model., Results: Among 9971 identified siblings, 2829 had been hospitalised for infections. The risk of infectious disease was increased among predisposed compared with non-predisposed in both biological (1.18; 95% confidence limits 1.03-1.36) and adoptive siblings (1.23; 0.98-1.53). The risk of a fatal outcome of the infections was strongly increased (9.36; 2.94-29.8) in biological full siblings, but such associations were not observed for the biological half siblings or for the adoptive siblings., Conclusion: Risk of getting infections appears to be weakly influenced by both genetically determined susceptibility to infection and by family environment, whereas there appears to be a strong non-additive genetic influence on risk of fatal outcome.

The Danish adoption register contains data on the 12 301 Danish nonfamilial adoptions during 1924-1947. From that register a case-cohort sample was selected consisting of all case adoptees, that is those adoptees dying before age 70 years, and a random sample of 1683 adoptees. The survival data of their biological and adoptive parents were collected with the purpose of studying the association of survival between the adoptee and his/her biological or adoptive parents. Motivated by this study, we explored how to make inference in a shared frailty model for case-cohort data. Our approach was to use inverse probability weighting to account for the sampling in a conditional, shared frailty Poisson model and to use the robust variance estimator proposed by Moger et al. (Statist. Med. 2008; 27:1062-1074).To explore the performance of the estimation procedure, a simulation study was conducted. We studied situations with three types of covariates: one with equal values between families (e.g. generation in parent-offspring pairs), an individual covariate, and one with equal values within each family (e.g. family size).The estimation of the frailty parameter tended to be unbiased; however, a small bias was seen for rare causes of death. The estimation of variance was unbiased when covariates were individual or equal within families, but some overestimation was seen when the covariate was equal between families. As in the earlier analyses, we found that there was a moderate genetic influence on the mortality rate, especially from all causes of death and vascular causes, and we found no effect of familial environment.

Background: There is a familial influence on risk of many diseases and on mortality in general, which, according to studies of twins, is due to a combination of genetic and environmental effects. Adoption studies, which rest on different assumptions, may also be used to estimate separately the genetic and environmental effects on rate of dying., Methods: The genetic influence on the rate of dying before age 70 years was investigated by estimation of the associations in total and cause-specific mortality of Danish adoptees and their biologic full and half siblings. Familial environmental influences shared at the same time in life were investigated in adoptees and their adoptive siblings. The study basis is the 14,425 nonfamilial adoptions formally granted in Denmark during the period 1924 through 1947, recorded in the Danish Adoption Register. From this register we selected the 1552 "case" adoptees (who died before 01 April 1993) and 1710 "noncase" adoptees alive at that date. The siblings of the case and noncase adoptees were traced in the archives and followed forward, and the rates of dying before age 70 years were compared., Results: Compared with mortality of the biologic siblings of noncase adoptees, the mortality of biologic siblings of dead adoptees was approximately 2-fold higher for death with infections and vascular causes, and around 45% increased for natural causes and for all causes., Conclusion: The results suggest that there is a genetic effect on the rate of death with infections, vascular causes, natural causes and all causes, whereas there is no indication of an influence of shared sibling environment.

Background: Genetic and maternal prenatal environmental factors as well as the post-natal rearing environment may contribute to the association between childhood socioeconomic circumstances and later mortality. In order to disentangle these influences, we studied all-cause and cause-specific mortality in a cohort of adoptees, in whom we estimated the effects of their biological and adoptive fathers' social classes as indicators of the genetic and/or prenatal environmental factors and the post-natal environment, respectively., Methods: In all 12 608 children born 1924-47 in Denmark who were placed early in life with adoptive parents were followed up for causes of death until 2000. Hazard ratios for paternal social class retrieved from adoption records were estimated using Cox regression models., Results: Adoptees with biological fathers from higher social classes had a lower rate of mortality after their fifth decade of life, mainly due to a lower risk of cardiovascular, infectious, and respiratory diseases. Adoptive father's social class showed no clear relation with adoptee's mortality risk. The risk estimates for paternal social class were slightly attenuated after adjustment for adoptee's adult social class, which as expected was inversely related to mortality from both natural and external causes., Conclusion: Genetic and/or prenatal environmental factors contribute to the development of the relation of paternal social class to mortality from natural causes later in adult life independently of the effect of own social class, whereas there is no evidence for such long-term effect of the rearing environment.

Objectives: To study if genes with common single nucleotide polymorphisms (SNPs) associated with obesity-related phenotypes influence weight loss (WL) in obese individuals treated by a hypo-energetic low-fat or high-fat diet., Design: Randomised, parallel, two-arm, open-label multi-centre trial., Setting: Eight clinical centres in seven European countries., Participants: 771 obese adult individuals., Interventions: 10-wk dietary intervention to hypo-energetic (-600 kcal/d) diets with a targeted fat energy of 20%-25% or 40%-45%, completed in 648 participants., Outcome Measures: WL during the 10 wk in relation to genotypes of 42 SNPs in 26 candidate genes, probably associated with hypothalamic regulation of appetite, efficiency of energy expenditure, regulation of adipocyte differentiation and function, lipid and glucose metabolism, or production of adipocytokines, determined in 642 participants., Results: Compared with the noncarriers of each of the SNPs, and after adjusting for gender, age, baseline weight and centre, heterozygotes showed WL differences that ranged from -0.6 to 0.8 kg, and homozygotes, from -0.7 to 3.1 kg. Genotype-dependent additional WL on low-fat diet ranged from 1.9 to -1.6 kg in heterozygotes, and from 3.8 kg to -2.1 kg in homozygotes relative to the noncarriers. Considering the multiple testing conducted, none of the associations was statistically significant., Conclusions: Polymorphisms in a panel of obesity-related candidate genes play a minor role, if any, in modulating weight changes induced by a moderate hypo-energetic low-fat or high-fat diet.

The associations in mortality of adult adoptees and their biological or adoptive parents have been studied in order to separate genetic and environmental influences. The 1003 Danish adoptees born 1924-26 have previously been analysed in a Cox regression model, using dichotomised versions of the parents' lifetimes as covariates. This model will be referred to as the conditional Cox model, as it analyses lifetimes of adoptees conditional on parental lifetimes. Shared frailty models may be more satisfactory by using the entire observed lifetime of the parents. In a simulation study, sample size, distribution of lifetimes, truncation- and censoring patterns were chosen to illustrate aspects of the adoption dataset, and were generated from the conditional Cox model or a shared frailty model with gamma distributed frailties. First, efficiency was compared in the conditional Cox model and a shared frailty model, based on the conditional approach. For data with type 1 censoring the models showed no differences, whereas in data with random or no censoring, the models had different power in favour of the one from which data were generated. Secondly, estimation in the shared frailty model by a conditional approach or a two-stage copula approach was compared. Both approaches worked well, with no sign of dependence upon the truncation pattern, but some sign of bias depending on the censoring. For frailty parameters close to zero, we found bias when the estimation procedure used did not allow negative estimates. Based on this evaluation, we prefer to use frailty models allowing for negative frailty parameter estimates. The conclusions from earlier analyses of the adoption study were confirmed, though without greater precision than using the conditional Cox model. Analyses of associations between parental lifetimes are also presented.

Genetic and environmental influence on risk of premature death in adulthood was investigated by estimating the associations in total and cause-specific mortality of adult Danish adoptees and their biological and adoptive parents. Among all 14,425 non-familial adoptions formally granted in Denmark during the period 1924 through 1947, we selected the study population according to a case-cohort sampling design. As the case-control design, the case-cohort design has the advantage of economic data collection and little loss in statistical efficiency, but the case-cohort sample has the additional advantages that rate ratio estimates may be obtained, and re-use of the cohort sample in future studies of other outcomes is possible. Analyses were performed using Kalbfleisch and Lawless's estimator for hazard ratio, and robust estimation for variances. In the main analyses the sample was restricted to birth years of the adoptees 1924 and after, and age of transfer to the adoptive parents before 7 years, and age at death was restricted to 16 to 70 years. The results showed a higher mortality among adoptees, whose biological parents died in the age range of 16 to 70 years; this was significant for deaths from natural causes, vascular causes and all causes. No influence was seen from early death of adoptive parents, regardless of cause of death., ((c) 2005 Wiley-Liss, Inc.)

Aim: The preventive effect of physical activity on risk of cancer in general remains controversial. This study aimed at assessment of the associations between leisure- time physical activity and incidence of cancer in the general population of adult men and women., Methods: 13,216 women and 18,718 men aged 20-93 years selected from the general population participated in a health examination including a questionnaire with information on physical activity, smoking, alcohol intake, postmenopausal hormones, and socioeconomic status. Incident cases of cancers where recorded during a follow-up period of 14 years. The six most frequent cancer cases in both sexes were included in this analysis., Results: A highly significant inverse association was seen between vigorous physical activity in leisure time and cancer of the ovary, adjusted rate ratio being 0.33 (95% CI 0.16-0.67; p = 0.001) for the most physical active women. In men there was a highly significant increase for non-melanoma skin cancer, with adjusted rate ratio of 1.72 (95% CI 1.23-2.40; p = 0.001), for the most active men and vigorous activity was associated with a non-significant lower risk of colon cancer, the adjusted rate ratio being 0.72 (95% CI 0.47-1.11; p = 0.06)., Conclusion: Generally, there were no, or only weakly, inverse associations between physical activity in leisure time and incidence of cancer, except for cancer of the ovary.

Objectives: This study aims at examining whether the relation between established risk factors and mortality differs with socioeconomic status as measured by level of education., Methods: A population-based sample of 14,399 women and 16,236 men aged 20-93 years from Copenhagen was stratified into three educational levels measured as basic schooling, and the effect of smoking habits, alcohol consumption, physical activity, and body mass index, respectively, on mortality was assessed., Results: Those with the lowest level of education were most frequently heavy smokers, heavy drinkers, physically inactive, and obese. During a mean follow up of 16 years 10,952 subjects died. Compared with subjects with the lowest educational level, women with the highest educational level had a relative risk of 0.80 (95% CI; 0.70-0.91), and men of 0.71 (0.65-0.78). Heavy smoking compared with never smoking implied a more than twofold increased risk at all three educational levels among both men and women. The relation between alcohol intake and mortality was J-shaped on all three educational levels. There were decreasing risk functions describing the relations between physical activity and mortality on all three strata. Further, subjects who were either very lean or obese had increased risks of death compared with those of normal weight at all educational levels in both genders., Conclusions: The difference in distribution of the main known risk factors may be part of the explanation for the differences in mortality risk. However, these risk factors seem to influence mortality equally at different educational levels. Therefore, social inequalities in mortality do not seem to be explained only by differences in effect of lifestyle risk factors, but are also related to the social rank or unexamined factors within., (Copyright 2004 Taylor & Francis)

A case-cohort sample of adoptees was collected to investigate genetic and environmental influences on premature death, which motivated us to supplement existing simulation results to explore the performance of various estimators proposed for case-cohort samples of survival data. We studied six regression coefficients estimators, which differ with regard to the weighting scheme used in a pseudo-likelihood function, and two different estimators of their variances. Compared to earlier simulation studies, we changed the following conditions: type of explanatory variable, the distribution of lifetimes, and the percentage of deaths in the full cohort. The latter condition affected the performance of the estimated variances of the regression coefficients, where we found a systematic bias of the estimator, proposed by Self and Prentice, dependent on the percentages of deaths. This dependence of percentages of death was different for different sizes of case-cohort studies. A robust variance estimator showed a better overall performance. The estimators of regression coefficients compared did not differ much, the estimators proposed by Kalbfleisch and Lawless and by Prentice performing very well. Results of the case-cohort data of adoptees were not in conflict with earlier findings of a moderate genetic influence on premature death in adulthood., (Copyright 2003 John Wiley & Sons, Ltd.)

Background: The inverse relation between ischaemic heart disease (IHD) and income is well known among men, but it remains to be clarified whether the relationship between social gradient and IHD is similar for men and women. The present study explores the associations between income and IHD in men and women in a Nordic country., Methods: We used data from two prospective population studies conducted in Copenhagen. A total of 22 782 subjects, 54% women, with initial examination between 1964 and 1992 were followed until 1996 for hospital admission or death from IHD. We performed survival analyses, taking traditional cardiovascular risk factors into account, and estimated IHD-free life expectancy by household income in men and women., Results: During follow-up, 1803 men and 1258 women experienced an event of IHD (21% fatal). The hazards by deciles of income showed a non-linear graded inverse effect of income, with a large group of middle-income in which income was not associated with risk of IHD. The hazard ratio for highest versus lowest deciles was 0.53 (95% CI: 0.44-0.65). The association was attenuated by adjustment for risk factors, but remained statistically significant. The associations were similar for both sexes. Median IHD-free life expectancy for low-income versus high-income groups was reduced by 9.4 and 7.0 years in men and women, respectively., Conclusions: The effect of household income on risk of IHD was graded and similar for men and women. The difference between high and low income, regarding IHD-free life expectancy, was considerable.

Genetic and environmental influence on risk of premature death in adulthood was investigated by estimating the associations in total and cause-specific mortality of adult Danish adoptees and their biological and adoptive parents. Among all 14,427 nonfamilial adoptions formally granted in Denmark during the period 1923 through 1947, we identified 976 case families in which the adoptee died before a fixed date. As control families, we selected 976 families where the adoptees were alive on that date, and matched to the case adoptees with regard to gender and year and month of birth. The data were viewed as a cohort of case parents and a cohort of control parents, and lifetime distributions in the two cohorts were compared using a Cox regression, stratified with regard to the matching variables: gender and year of birth. In the main analyses, the sample was restricted with regard to birth year of the adoptees, and age of transfer to the adoptive parents, and age at death was restricted to the same range for parents and offspring (25-64 years) in order to consider a symmetric lifetime distribution. This reduces the sample to 459 case families and 738 control families. Various truncations, restrictions, and stratifications were used in order to examine the robustness of the results. The results showed a higher mortality among biological parents who had children dying in the age range 25 through 64 years, and this was significant for death from natural causes, infectious causes, vascular causes, and from all causes combined. There were no significant effects for the adoptive parents. This study supports that there are moderate genetic influences on the risk of dying prematurely in adulthood, and only a small, if any, effect of the family environment., (Copyright 2002 Wiley-Liss, Inc.)

Objective: To study the influence of scan velocities of DXA on the measured size of fat mass, lean body mass, bone mineral content and density, and total body weight., Research Methods and Procedures: The subjects were 71 healthy white adults, 38 women and 33 men. The mean age was 41.7 +/- 13.5 years and body mass index was 28.6 +/- 5.6 kg/m(2). The subjects were scanned consecutively in slow, medium, and fast scan mode by a Lunar DPX-IQ DXA scanner., Results: Throughout the body mass index and sagittal height ranges, scanned lean body mass significantly decreased with higher scan velocity and lean body mass was 2.7% lower in fast than in medium mode (p < 0.0001). In contrast, fat mass, percentage of body fat, and bone mineral contents were higher with increasing scan velocity. Areas not analyzed by the scanner, so called blue spots, increased with scan velocity and sagittal height, and their presence significantly enhanced the error. Body weight estimated by DXA in slow mode was -0.8% lower than scale weight in the women (p < 0.001) and -0.2% in men (not significant), and the difference was greater with increasing scan velocity., Discussion: Scan velocity significantly influences the measured fat mass size, lean body mass, bone mineral content, and body weight. To obtain the most accurate results, slow mode is preferable and fast scans should be avoided. Future studies should report and take scan velocity into consideration.