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OBJECTIVES: Maternal body mass index (BMI), birth weight, and preschool BMI may help identify children at high risk of overweight as they are (1) similarly linked to adolescent overweight at different stages of the obesity epidemic, (2) linked to adult obesity and metabolic alterations, and (3) easily obtainable in health examinations in young children. The aim was to develop early childhood prediction models of adolescent overweight, adult overweight, and adult obesity.METHODS: Prediction models at various ages in the Northern Finland Birth Cohort born in 1966 (NFBC1966) were developed. Internal validation was tested using a bootstrap design, and external validation was tested for the model predicting adolescent overweight using the Northern Finland Birth Cohort born in 1986 (NFBC1986).RESULTS: A prediction model developed in the NFBC1966 to predict adolescent overweight, applied to the NFBC1986, and aimed at labelling 10% as "at risk" on the basis of anthropometric information collected until 5 years of age showed that half of those at risk in fact did become overweight. This group constituted one-third of all who became overweight.CONCLUSIONS: Our prediction model identified a subgroup of children at very high risk of becoming overweight, which may be valuable in public health settings dealing with obesity prevention.

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.

Advanced paternal age (APA) and intelligence quotient (IQ) are both associated with the risk of schizophrenia spectrum disorder (SSD) in young adult offspring. We hypothesized that the offspring SSD risk gradient associated with paternal age is mediated by offspring IQ. We investigated joint and separate associations of paternal age and offspring IQ with the risk of SSD. We used IQ routinely measured at conscription in Danish males (n=138,966) from cohorts born in 1955-84 and in 1976-1993 and followed them from a year after the conscription through 2010. We used Cox regression to estimate the incidence rate ratio (IRR) of SSD. During the follow-up, 528 men developed SSD (incidence rate [IR] 5.2 and 8.6 per 10,000 person-years in the first and second cohorts, respectively). APA was associated with higher risk of SSD (IRR, 1.32; 95% CI, 1.10-1.60 per a ten-year increase in paternal age). A higher IQ was associated with lower SSD risk (IRR, 0.68; 95% confidence interval [CI], 0.63-0.74 per one SD increase). The IR of SSD was higher among persons who were draft-exempt for health reasons (<20% of the men). Overall, there was little evidence of lower premorbid IQ in APA-related SSD (individuals who developed SSD and were also offspring of older fathers). Our results do not support the notion that risk gradient for offspring SSD associated with paternal age is mediated by offspring IQ.

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.

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.

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).

Udgivelsesdato: 2010-Mar, 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.

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.

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.

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.

survival analysis; Cox proportional hazard; Kalbfleisch and Lawless estimator; cause-specific deaths