The intergenerational resemblance in body mass index may have increased during the development of the obesity epidemic due to changes in environment and/or expression of genetic predisposition.
This study investigates trends in intergenerational correlations of childhood body mass index (BMI; kg/m2) during the emergence of the obesity epidemic.
The study population was derived from the Copenhagen School Health Records Register, which includes height and weight measurements since birth year 1930. Mothers and fathers with BMIs available at ages 7 (n = 25,923 and n = 20,972) or 13 years (n = 26,750 and n = 21,397), respectively, were linked through the civil registration system introduced in 1968 to their children with BMIs available at age 7 years. Age- and sex-specific BMI z-scores were calculated. Correlations were estimated across eight intervals of child birth years (1952–1989) separately by sex. Trends in these correlations were examined. Whereas the mother-child correlations reflected the biological relationship, a likely decline in the assignment of non-biological fathers through the registration system across time must be considered when interpreting the father-child correlations.
The BMI correlations between mothers and sons ranged from 0.29–0.36 and they decreased marginally, albeit significantly across time at ages 7–7 years (−0.002/year, p = 0.006), whereas those at 13–7 years remained stable (<0.0004/year, p = 0.96). Mother-daughter correlations ranged from 0.30–0.34, and they were stable at ages 7–7 years (0.0001/year, p = 0.84) and at 13–7 years (0.0004/year, p = 0.56). In contrast, father-son correlations increased significantly during this period, both at ages 7–7 (0.002/year, p = 0.007) and at ages 13–7 years (0.003/year, p<0.001), whereas the increase in father-daughter correlations were insignificant both at ages 7–7 (0.001/year, p = 0.37) and at ages 13–7 years (0.001/year, p = 0.18).
During the obesity epidemics development, the intergenerational resemblance with mothers remained stable, whereas the father-child BMI resemblance increased, possibly reflecting changes in family relationships, and unlikely to have influenced the epidemic.
To assess long-term, cause-specific mortality rates and rate ratios of the patients alive at 1 year after subarachnoid hemorrhage (SAH).
The population-based, prospective, cohort study with a nested case-control design consisted of 64,349 persons (aged 25–74 years at enrollment) who participated in the National FINRISK Study between 1972 and 2007. Four hundred thirty-seven SAH cases, 233 one-year SAH survivors, and their matched intrinsic controls were identified and followed up until the end of 2009 through the nationwide Finnish Causes of Death Register. All-cause mortality rates and rate ratios of the 1-year SAH survivors and controls were the main outcome measures.
Eighty-eight (37.8%) of 233 one-year SAH survivors died during the total follow-up time of 2,487 person-years (median 8.6 years, range 0.1–35.8 years). The 1-year SAH survivors had a hazard ratio of 1.96 (95% confidence interval 1.57–2.47) for death compared with the matched general population with 10 controls for each SAH survivor. One-year SAH survivors had up to 31 additional deaths per 1,000 person-years compared with controls with minimal cerebrovascular risk factors. The higher long-term risk of death among SAH survivors was attributed solely to cerebrovascular diseases, and most important modifiable risk factors for death were smoking, high systolic blood pressure (≥159 mm Hg), and high cholesterol levels (≥7.07 mmol/L).
One-year SAH survivors have excess mortality, which is attributed to an exceptional risk of deadly cerebrovascular events. Aggressive post-SAH cerebrovascular risk factor intervention strategies are highly warranted.
Occupational class differences in body mass index (BMI) have been systematically reported in developed countries, but the studies have mainly focused on white populations consuming a Westernized diet. We compared occupational class differences in BMI and BMI change in Japan and Finland.
The baseline surveys were conducted during 1998–1999 among Japanese (n = 4080) and during 2000–2002 among Finnish (n = 8685) public-sector employees. Follow-up surveys were conducted among those still employed, in 2003 (n = 3213) and 2007 (n = 7086), respectively. Occupational class and various explanatory factors were surveyed in the baseline questionnaires. Linear regression models were used for data analysis.
BMI was higher at baseline and BMI gain was more rapid in Finland than in Japan. In Finland, baseline BMI was lowest among men and women in the highest occupational class and progressively increased to the lowest occupational class; no gradient was found in Japan (country interaction effect, P = 0.020 for men and P < 0.0001 for women). Adjustment for confounding factors reflecting work conditions and health behavior increased the occupational class gradient among Finnish men and women, whereas factors related to social life had no effect. No statistically significant difference in BMI gain was found between occupational classes.
The occupational class gradient in BMI was strong among Finnish employees but absent among Japanese employees. This suggests that occupational class inequalities in obesity are not inevitable, even in high-income societies.
occupational class; body mass index; weight gain; international comparisons
Secular trends towards earlier puberty, possibly caused by new environmental triggers, provide a basis for periodic evaluation of the influence and interaction of genetic and environmental effects on pubertal timing. In such studies, a practical marker that reflects timing of puberty in both genders needs to be used. We investigated genetic and environmental influences on pubertal timing by using change in the relative height between early and late adolescence (HD:SDS, height difference in standard deviations) as a new marker of pubertal timing. HD:SDS correlated well with age at peak height velocity in a population of men and women with longitudinal growth data. In 2,309 twin girls and 1,828 twin boys, HD:SDS was calculated between height SDs at age 11.5 and 17.5, and 14.0 and 17.5 years, respectively. Quantitative genetic models for twin data were fitted to estimate the genetic contribution to HD:SDS. We also investigated whether the same genetic factors influenced individual differences between HD:SDS and development of secondary sex characteristics prospectively collected by pubertal development scale (PDS). Genetic effects contributed to 86 and 82% of the variance in HD:SDS in girls and boys, respectively, when using the same model including additive genetic and specific environmental factors. In girls, 30% and in boys, 49% of the genetic factors affecting PDS and HD:SDS were the same. Future comparison of the results of periodic evaluations allows estimation of possible changes in the effects of environment on timing of puberty. In such studies, HD:SDS can be used as a practical marker of pubertal timing.
Prospective studies on the risk factors for subarachnoid hemorrhage (SAH) are limited. Moreover, the effect of risk factors on the incidence rates of SAH is not well known about.
In this study, we aimed to identify risk factors for SAH and characterize subgroups in a population with a high incidence of SAH.
After recording multiple potential risk factors for SAH at the time of enrolment, first ever SAH events between 1972 and 2009 were recorded through the nationwide Causes of Death Register and Hospital Discharge Register for the population-based cohort of 64 349 participants, who participated in the National FINRISK Study between 1972 and 2007 in Finland.
During the follow-up time of 1.26 million person-years (median 17.9 years, range 0 to 37.9 years), 437 persons experienced fatal or non-fatal SAH. Crude SAH incidence was 34.8 (95% confidence interval: 31.7–38.2) per 100 000 person-years among ≥25-year-old persons. Female sex, high blood pressure values and current smoking were confirmed as risk factors for SAH. Previous myocardial infarction, history of premature stroke (any kind) in mother and elevated cholesterol levels in men were identified as new risk factors for SAH. Depending on the combination of risk factors, SAH incidence varied between 8 and 171 per 100 000 person-years.
New and previously reported risk factors appear to have a much stronger association with the incidence of SAH than is ordinarily seen in cardiovascular diseases. Risk factor assessments may facilitate the identification of high-risk persons who should be the focus of preventive interventions.
► Associations of exposures with mortality may be confounded by existing ill health. ► We used a son's height as an instrument for parents’ height to avoid confounding. ► Parents of taller sons had lower cardiovascular and respiratory disease mortality. ► Parents of taller sons had higher mortality from cancer. ► Previous studies of height are not substantially confounded by existing ill health.
Height is associated with mortality from many diseases, but it remains unclear whether the association is causal or due to confounding by social factors, genetic pleiotropy,1 or existing ill-health. The authors investigated whether the association of height with mortality is causal by using a son's height as an instrumental variable (IV) for parents’ height among the parents of a cohort of 1,036,963 Swedish men born between 1951 and 1980 who had their height measured at military conscription, aged around 18, between 1969 and 2001. In a two-sample IV analysis adjusting for son's age at examination and secular trends in height, as well as parental age, and socioeconomic position, the hazard ratio (HR) for all-cause paternal mortality per standard deviation (SD, 6.49 cm) of height was 0.96 (95% confidence interval (CI): 0.95, 0.96). The results of IV analyses of mortality from all causes, cardiovascular disease (CVD), respiratory disease, cancer, external causes and suicide were comparable to those obtained using son's height as a simple proxy for own height and to conventional analyses of own height in the present data and elsewhere, suggesting that such conventional analyses are not substantially confounded by existing ill-health.
IV, instrumental variable; HR, hazard ratio; SD, standard deviation; CI, confidence interval; CVD, cardiovascular disease; BMI, body mass index; SEP, socioeconomic position; CHD, coronary heart disease; Body height; Mortality; Confounding factor; Causality; Cohort studies
We analyzed the association between mean height and old age cognition in two Nordic twin cohorts with different childhood living conditions. The cognitive performance of 4720 twin individuals from Denmark (mean age 81.6 years, SD = 4.59) and Finland (mean age 74.4 years, SD = 5.26) was measured using validated cognitive screens. Taller height was associated with better cognitive performance in Finland (β-estimates 0.18 SD/10cm, p value < .001, for men and 0.13 SD, p = .008, for women), but this association was not significant in Denmark (β-estimates 0.0093 SD, p value = .16, for men and 0.0075 SD, p value = .016, for women) when adjusted for age and education/social class. Among Finnish participants higher variability of cognitive performance within shorter height quintiles was observed. Analysis using gene-environment interaction models showed that environmental factors exerted a greater impact on cognitive performance in shorter participants, whereas in taller participants' it was explained mainly by genetic factors. Our results suggest that shorter participants with childhood adversity are more vulnerable to environmental risk factors for cognitive impairment.
twins; genetics; height; cognition; dementia; risk factor
Birth order has been suggested to be linked to several cardiovascular disease (CVD) risk factors, but the evidence is still inconsistent. We aim to determine the associations of birth order with body mass index (BMI), muscle strength and blood pressure. Further we will analyse whether these relationships are affected by family characteristics.
BMI, elbow flexion, hand grip and knee extension strength and systolic and diastolic blood pressure were measured at conscription examination in 1 065 710 Swedish young men born between 1951 and 1975. The data were analysed using linear multivariate and fixed effects regression models; the latter compare siblings and account for genetic and social factors shared by brothers.
Fixed effect regression analysis showed that birth order was inversely associated with BMI: second and third born had 0.8% and 1.1% (p<0.001) lower BMI than first-born, respectively. The association pattern differed among muscle strengths. After adjustment for BMI, first-born presented lower elbow flexion and hand grip strength than second-born (−5.9 N and −3.8 N, respectively, p<0.001). Knee extension strength was inversely related to birth order though not always significantly. The association between birth order and blood pressure was not significant.
Birth order is negatively associated with BMI and knee extension strength, positively with elbow flexion and hand grip strength, and is not associated with blood pressure among young men. Although the effects are small, the link between birth order and some CVD risk factors is already detectable in young adulthood.
Associations of height and head circumference with IQ are well documented, but much less is known about the association of IQ with other anthropometric measures or the mechanisms behind these associations. We therefore analyzed the associations between IQ and several anthropometric measures using a twin-study design. Twins born in Minnesota were assessed at either age 11 (756 complete pairs) or 17 (626 complete pairs) and analyzed using genetic modeling. Head circumference and height showed the most consistent positive associations with IQ, whereas more detailed anthropometric measures were not significantly better predictors of IQ. These associations were mainly due to common genetic factors. Our results suggest that the same genetic factors have an effect on physical and cognitive development. Head circumference and height capture information on children’s physical development, which is partly associated also with cognitive development.
IQ; genetic factors; height; head circumference; children; twins
Early pubertal onset in females is associated with increased risk for adult obesity and cardiovascular disease, but whether this relationship is independent of preceding childhood growth events is unclear. Furthermore, the association between male puberty and adult disease remains unknown. To clarify the link between puberty and adult health, we evaluated the relationship between pubertal timing and risk factors for type 2 diabetes and cardiovascular disease in both males and females from a large, prospective, and randomly ascertained birth cohort from Northern Finland.
RESEARCH DESIGN AND METHODS
Pubertal timing was estimated based on pubertal height growth in 5,058 subjects (2,417 males and 2,641 females), and the relationship between puberty and body weight, glucose and lipid homeostasis, and blood pressure at age 31 years was evaluated with linear regression modeling.
Earlier pubertal timing associated with higher adult BMI, fasting insulin, diastolic blood pressure, and decreased HDL cholesterol in both sexes (P < 0.002) and with higher total serum cholesterol, LDL cholesterol, and triglycerides in males. The association with BMI and diastolic blood pressure remained statistically significant in both sexes, as did the association with insulin levels and HDL cholesterol concentrations in males after adjusting for covariates reflecting both fetal and childhood growth including childhood BMI.
We demonstrate independent association between earlier pubertal timing and adult metabolic syndrome-related derangements both in males and females. The connection emphasizes that the mechanisms advancing puberty may also contribute to adult metabolic disorders.
Background: The genetic predisposition to obesity may have contributed to the obesity epidemic through assortative mating. We investigated whether spouses were positively assorted by body mass index (BMI; = kg/m2) in late childhood, and whether changes in assorted marriage by upper BMI-percentiles occurred during the obesity epidemic. Methods: In the Copenhagen School Health Records Register (CSHRR) boys and girls with measures of BMI at age 13 years later became 37,792 spousal-pairs who married between 1945 and 2010. Trends in the spousal BMI correlations using sex-, age-, and birth cohort-specific BMI z-scores across time were investigated. Odds ratios (ORs) of marriage among spouses both with BMI z-scores >90th or >95th percentile compared with marriage among spouses ≤90th percentile were analyzed for marriages entered during the years prior to (1945–1970), and during the obesity epidemic (1971–2010). Findings: Spousal BMI correlations were around 0.05 and stayed similar across time. ORs of marriage among spouses with BMIs >90th percentile at age 13 were 1.21, 1.05–1.39, in 1945–1970, and increased to 1.63, 1.40–1.91, in 1971–2010 (p = 0.006). ORs of marriage among spouses both >95th BMI percentile were higher and increased more; from 1.39, 1.10–1.81, to 2.39, 1.85–3.09 (p = 0.004). Interpretation: Spousal correlations by pre-marital BMIs were small and stable during the past 65 years. Yet, there were assorted marriages between spouses with high BMI at age 13 years and the tendency increased alongside with the obesity epidemic which may increase the offsprings' predisposition to obesity.
assortative mating; body mass index; childhood; obesity; overweight; phenotype; human genetics
Adult height is inversely associated with the risk of coronary heart disease (CHD), but it is still unknown which phase of the human growth period is critical for the formation of this association. We investigated the association between growth in height from 7 to 13 years of age and the risk of CHD in adulthood.
Methods and Findings
The heights of almost all children born 1930 through 1976 who attended school in the Copenhagen municipality (232,063 children) were measured annually from 7 to 13 years of age. Birth weight data were available since 1936. Fatal and non-fatal CHD events were ascertained by register linkage until 2008 (25,214 cases). Hazard ratios (HR) with 95% confidence intervals (CI) were estimated by Cox proportional hazards regression for height z-scores (standard deviation units) and change in height z-scores. Height z-scores were inversely related to the risk of CHD. The association was strongest at 7 years of age (HR = 0.91, CI 0.90–0.92 in boys and 0.88, CI 0.86–0.90 in girls) and steadily weakened thereafter, yet it still remained at 13 years of age (HR = 0.95, CI 0.94–0.97 and 0.91, CI 0.89–0.93, boys and girls respectively). The associations were not modified by birth weight. Independent of the age-specific risk, rapid growth was associated with an increased CHD risk, most pronounced between 9 and 11 years in girls (HR = 1.22, CI 1.14–1.31) and between 11 and 13 years in boys (HR = 1.28, CI 1.22–1.33) per unit increase in z-score. Adjustment for body mass index somewhat strengthened the associations of CHD risk with height and weakened the association with growth.
Risk of CHD in adulthood is inversely related to height at ages 7 through 13 years, but strongest in the youngest, and, independently hereof, the risk increased by growth velocity.
Average physical stature has increased dramatically during the 20th century in many populations across the world with few exceptions. It remains unclear if social inequalities in height persist despite improvements in living standards in the welfare economies of Western Europe. We examined trends in the association between height and socioeconomic indicators in adults over three decades in France. The data were drawn from the French Decennial Health Surveys: a multistage, stratified, random survey of households, representative of the population, conducted in 1970, 1980, 1991, and 2003. We categorised age into 10-year bands, 25–34, 35–44, 45–54 and 55–64 years. Education and income were the two socioeconomic measures used. The slope index of inequality (SII) was used as a summary index of absolute social inequalities in height. The results show that average height increased over this period; men and women aged 25–34 years were 171.9 and 161.2 cm tall in 1970 and 177.0 and 164.0 cm in 2003. However, education-related inequalities in height remained unchanged over this period and in men were 4.48 cm (1970), 4.71 cm (1980), 5.58 cm (1991) and 4.69 cm (2003), the corresponding figures in women were 2.41, 2.37, 3.14 and 2.96 cm. Income-related inequalities in height were smaller and much attenuated after adjustment for education. These results suggest that in France, social inequalities in adult height in absolute terms have remained unchanged across the three decades under examination.
height; trends; social inequalities
Background and Objectives
There is no doubt that the dramatic worldwide increase in obesity prevalence is due to changes in environmental factors. However, twin and family studies suggest that genetic differences are responsible for the major part of the variation in adiposity within populations. Recent studies show that the genetic effects on body mass index (BMI) may be stronger when combined with presumed risk factors for obesity. We tested the hypothesis that the genetic variance of BMI has increased during the obesity epidemic.
The data comprised height and weight measurements of 1,474,065 Swedish conscripts at age 18–19 y born between 1951 and 1983. The data were linked to the Swedish Multi-Generation Register and the Swedish Twin Register from which 264,796 full-brother pairs, 1,736 monozygotic (MZ) and 1,961 dizygotic (DZ) twin pairs were identified. The twin pairs were analysed to identify the most parsimonious model for the genetic and environmental contribution to BMI variance. The full-brother pairs were subsequently divided into subgroups by year of birth to investigate trends in the genetic variance of BMI.
The twin analysis showed that BMI variation could be explained by additive genetic and environmental factors not shared by co-twins. On the basis of the analyses of the full-siblings, the additive genetic variance of BMI increased from 4.3 [95% CI 4.04–4.53] to 7.9 [95% CI 7.28–8.54] within the study period, as did the unique environmental variance, which increased from 1.4 [95% CI 1.32–1.48] to 2.0 [95% CI 1.89–2.22]. The BMI heritability increased from 75% to 78.8%.
The results confirm the hypothesis that the additive genetic variance of BMI has increased strongly during the obesity epidemic. This suggests that the obesogenic environment has enhanced the influence of adiposity related genes.
Previous studies of risk factors for disability pension (DP) have mainly focused on psychosocial, or environmental, factors, while the relative importance of genetic effects has been less studied. Sex differences in biological mechanisms have not been investigated at all.
The study sample included 46,454 Swedish twins, consisting of 23,227 complete twin pairs, born 1928–1958, who were followed during 1993–2008. Data on DP, including diagnoses, were obtained from the National Social Insurance Agency. Within-pair similarity in liability to DP was assessed by calculating intraclass correlations. Genetic and environmental influences on liability to DP were estimated by applying discrete-time frailty modeling.
During follow-up, 7,669 individuals were granted DP (18.8% women and 14.1% men). Intraclass correlations were generally higher in MZ pairs than DZ pairs, while DZ same-sexed pairs were more similar than opposite-sexed pairs. The best-fitting model indicated that genetic factors contributed 49% (95% CI: 39–59) to the variance in DP due to mental diagnoses, 35% (95% CI: 29–41) due to musculoskeletal diagnoses, and 27% (95% CI: 20–33) due to all other diagnoses. In both sexes, genetic effects common to all ages explained one-third, whereas age-specific factors almost two-thirds, of the total variance in liability to DP irrespective of diagnosis. Sex differences in liability to DP were indicated, in that partly different sets of genes were found to operate in women and men, even though the magnitude of genetic variance explained was equal for both sexes.
The findings of the study suggest that genetic effects are important for liability to DP due to different diagnoses. Moreover, genetic contributions to liability to DP tend to differ between women and men, even though the overall relative contribution of genetic influences does not differ by sex. Hence, the pathways leading to DP might differ between women and men.
Background and objectives
There is no doubt that the dramatic worldwide increase in obesity prevalence is due to changes in environmental factors. However, twin studies suggest that genetic differences are responsible for the major part of the variation in body mass index (BMI) and other measures of body fatness within populations. Several recent studies suggest that the genetic effects on adiposity may be stronger when combined with presumed risk factors for obesity. We tested the hypothesis that a higher prevalence of obesity and overweight and a higher BMI mean is associated with a larger genetic variation in BMI.
The data consisted of self-reported height and weight from two Danish twin surveys in 1994 and 2002. A total of 15,017 monozygotic and dizygotic twin pairs were divided into subgroups by year of birth (from 1931 through 1982) and sex. The genetic and environmental variance components of BMI were calculated for each subgroup using the classical twin design. Likewise, the prevalence of obesity, prevalence of overweight and the mean of the BMI distribution was calculated for each subgroup and tested as explanatory variables in a random effects meta-regression model with the square root of the additive genetic variance (equal to the standard deviation) as the dependent variable.
The size of additive genetic variation was positively and significantly associated with obesity prevalence (p = 0.001) and the mean of the BMI distribution (p = 0.015). The association with prevalence of overweight was positive but not statistically significant (p = 0.177).
The results suggest that the genetic variation in BMI increases as the prevalence of obesity, prevalence of overweight and the BMI mean increases. The findings suggest that the genes related to body fatness are expressed more aggressively under the influence of an obesity-promoting environment.
Educational attainment, the highest degree or level of schooling obtained, is associated with important life outcomes, at both the individual level and the group level. Because of this, and because education is expensive, the allocation of education across society is an important social issue. A dynamic quantitative environmental-genetic model can help document the effects of social allocation patterns. We used this model to compare the moderating effect of general intelligence on the environmental and genetic factors that influence educational attainment in Sweden and the U.S. state of Minnesota. Patterns of genetic influence on educational outcomes were similar in these two regions, but patterns of shared environmental influence differed markedly. In Sweden, shared environmental influence on educational attainment was particularly important for people of high intelligence, whereas in Minnesota, shared environmental influences on educational attainment were particularly important for people of low intelligence. This difference may be the result of differing access to education: state-supported access (on the basis of ability) to a uniform higher-education system in Sweden, versus family-supported access to a more diverse higher-education system in the United States.
educational attainment; intelligence; gene-environment interaction; gene-environment correlation; genetic and environmental influences
Previous studies have shown that age, physical and mental health status and working circumstances, along with different socio-economic and psychosocial factors affect the retirement process. However, the role of psychological resources, such as sense of coherence (SOC), on the retirement process is still poorly understood. This study investigated the associations between SOC and intentions to retire early and whether these associations were explained by socio-economic, psychosocial and work and health related factors.
The data were derived from the Finnish Health and Social Support (HeSSup) Study. The information was gathered from postal surveys in 1998 (baseline) and in 2003 (follow-up). The analyzed data consisted of 7409 women and 4866 men aged 30-54 at baseline. SOC and background factors including childhood circumstances, language, education, working circumstances, social support, health behaviour and somatic and mental health status were assessed at baseline. The intentions to retire early were assessed at follow-up using logistic regression analysis.
SOC was associated with intentions to retire early among both genders. Socio-economic, psychosocial and work and health behaviour related factors did not influence the association between SOC and intentions to retire early among women and men reporting somatic or mental illness. Further, the association between SOC and intentions to retire early remained among (somatically and mentally) healthy men. Among healthy women the association was weaker and statistically non-significant. Among unhealthy women, the odds ratios of SOC was 0.97 (CI 95% 0.96-0.98) and 0.97 among ill men (CI 95% 0.96-0.98), i.e., each additional SOC score reduced the risk of intentions by 3% among both genders.
Unhealthy employees with low SOC and low education were in the greatest risk to have reported intentions to retire early. SOC had an independent effect on intentions to retire early, and a strong SOC may have a potential to prevent early retirement in groups otherwise at risk. An important challenge would be to target the resources of SOC to the most vulnerable and design appropriate interventions in order to strengthen the level of SOC and hence prolong working years of the aging employees.
AKT1, encoding the protein kinase B, has been associated with the genetic etiology of schizophrenia and bipolar disorder. However, minuscule data exist on the role of different alleles of in measurable quantitative endophenotypes, such as cognitive abilities and neuroanatomical features, showing deviations in schizophrenia and bipolar disorder. We evaluated the contribution of AKT1 to quantitative cognitive traits and 3D high-resolution neuroanatomical images in a Finnish twin sample consisting of 298 twins: 61 pairs with schizophrenia (8 concordant), 31 pairs with bipolar disorder (5 concordant) and 65 control pairs matched for age, sex and demographics. An AKT1 allele defined by the SNP rs1130214 located in the UTR of the gene revealed association with cognitive traits related to verbal learning and memory (P=0.0005 for a composite index). This association was further fortified by a higher degree of resemblance of verbal memory capacity in pairs sharing the rs1130214 genotype compared to pairs not sharing the genotype. Furthermore, the same allele was also associated with decreased gray matter density in medial and dorsolateral prefrontal cortex (P < 0.05). Our findings support the role of AKT1 in the genetic background of cognitive and anatomical features, known to be affected by psychotic disorders. The established association of the same allelic variant of AKT1 with both cognitive and neuroanatomical aberrations could suggest that AKT1 exerts its effect on verbal learning and memory via neural networks involving prefrontal cortex.
AKT1; quantitative trait loci; magnetic resonance imaging; association
To study genetic and environmental factors affecting body mass index (BMI) and BMI phenotypic correlations across adolescence.
Prospective, population-based, twin cohort study.
Subjects and methods
We used twin modeling in 2413 monozygotic and same-sex and opposite-sex dizygotic Finnish twin pairs born in 1983–1987 and assessed by self-report questionnaires at 11–12, 14, and 17 years.
Heritability of BMI was estimated to be 0.58–0.69 among 11–12- and 14-year-old boys and girls, 0.83 among 17-year-old boys and 0.74 among girls. Common environmental effects shared by siblings were 0.15–0.24 among 11–12- and 14-year-old boys and girls but no longer discernible at 17 y. Unique environmental effects were 0.15–0.23. Additive genetic factors explained 90–96% of the BMI phenotypic correlations across adolescence, whereas unique environmental factors explained the rest. Common environment had no effect on BMI phenotypic correlations.
The genetic contribution to BMI is strong during adolescence, and it mainly explains BMI phenotypic correlations across adolescence. Common environmental factors have an effect on BMI during early adolescence, but that effect disappears by late adolescence.
body mass index; adolescent; twins; genetics; growth and development; sex specific effects
No previous studies on the effect of genetic factors on the liability to disability retirement have been carried out. The main aim of this study was to investigate the contribution of genetic factors on disability retirement due to the most common medical causes, including depressive disorders.
The study sample consisted of 24 043 participants (49.7% women) consisting of 11 186 complete same-sex twin pairs including 3519 monozygotic (MZ) and 7667dizygotic (DZ) pairs. Information on retirement events during 1.1.1975–31.12.2004, including disability pensions (DPs) with diagnoses, was obtained from the Finnish nationwide official pension registers. Correlations in liability for MZ and DZ twins and discrete time correlated frailty model were used to investigate the genetic liability to age at disability retirement.
The 30 year cumulative incidence of disability retirement was 20%. Under the best fitting genetic models, the heritability estimate for DPs due to any medical cause was 0.36 (95% CI 0.32–0.40), due to musculoskeletal disorders 0.37 (0.30–0.43), cardiovascular diseases 0.48 (0.39–0.57), mental disorders 0.42 (0.35–0.49) and all other reasons 0.24 (0.17–0.31). The effect of genetic factors decreased with increasing age of retirement. For DP due to depressive disorders, 28% of the variance was explained by environmental factors shared by family members (95% CI 21–36) and 58% of the variance by the age interval specific environmental factors (95% CI 44–71).
A moderate genetic contribution to the variation of disability retirement due to any medical cause was found. The genetic effects appeared to be stronger at younger ages of disability retirement suggesting the increasing influence of environmental factors not shared with family members with increasing age. Familial aggregation in DPs due to depressive disorders was best explained by the common environmental factors and genetic factors were not needed to account for the pattern of familial aggregation.
We analysed genetic and environmental influences on self-esteem and its stability across adolescence.
Finnish twins born in 1983–1987 were assessed by questionnaire at ages 14y (N= 4132 twin individuals) and 17y (N=3841 twin individuals). Self esteem was measured using the Rosenberg global self-esteem scale and analyzed using quantitative genetic methods for twin data in the Mx statistical package.
The heritability of self-esteem was 0.62 (95% CI 0.56–0.68) in 14-y-old boys and 0.40 (95% CI 0.26–0.54) in 14-y-old girls, while the corresponding estimates at age 17y were 0.48 (95% CI 0.39–0.56) and 0.29 (95% CI 0.11–0.45). Rosenberg self-esteem scores at age 14 y and 17 y were modestly correlated (r=0.44 in boys, r=0.46 in girls). In boys, the correlation was mainly (82%) due to genetic factors, with residual co-variation due to unique environment. In girls, genetic (31%) and common environmental (61%) factors largely explained the correlation.
In adolescence, self-esteem seems to be differently regulated in boys versus girls. A key challenge for future research is to identify environmental influences contributing to self-esteem during adolescence and how these factors interact with genetic influences.
Self-esteem; twin study; longitudinal study; adolescence
Twin cohorts provide a unique advantage for investigations of the role of genetics and environment in the etiology of variation in common complex traits by reducing the variance due to environment, age, and cohort differences. The GenomEUtwin (http://www.genomeutwin.org) consortium consists of eight twin cohorts (Australian, Danish, Dutch, Finnish, Italian, Norwegian, Swedish, and United Kingdom) with the total resource of hundreds of thousands of twin pairs. We performed quantitative trait locus (QTL) analysis of one of the most heritable human complex traits, adult stature (body height) using genome-wide scans performed for 3,817 families (8,450 individuals) derived from twin cohorts from Australia, Denmark, Finland, Netherlands, Sweden, and United Kingdom with an approximate ten-centimorgan microsatellite marker map. The marker maps for different studies differed and they were combined and related to the sequence positions using software developed by us, which is publicly available (https://apps.bioinfo.helsinki.fi/software/cartographer.aspx). Variance component linkage analysis was performed with age, sex, and country of origin as covariates. The covariate adjusted heritability was 81% for stature in the pooled dataset. We found evidence for a major QTL for human stature on 8q21.3 (multipoint logarithm of the odds 3.28), and suggestive evidence for loci on Chromosomes X, 7, and 20. Some evidence of sex heterogeneity was found, however, no obvious female-specific QTLs emerged. Several cohorts contributed to the identified loci, suggesting an evolutionarily old genetic variant having effects on stature in European-based populations. To facilitate the genetic studies of stature we have also set up a website that lists all stature genome scans published and their most significant loci (http://www.genomeutwin.org/stature_gene_map.htm).
Twin cohorts provide a unique advantage for research of the role of genetics and environment behind common complex traits by reducing the variance due to environment, age, and cohort differences. The GenomEUtwin consortium consists of eight twin cohorts with the total resource of hundreds of thousands of twin pairs (http://www.genomeutwin.org). We performed quantitative family-based genetic linkage analysis for one of the most heritable human complex traits, adult stature (body height), using genome-wide scans derived from twin cohorts from Australia, Denmark, Finland, Netherlands, Sweden, and United Kingdom. Age, sex, and country were adjusted for in the data analyses. Human stature was found to be very heritable across all the cohorts and in the combined dataset. We found evidence for a shared genetic locus accounting for human stature on Chromosome 8, and suggestive evidence for loci on Chromosomes X, 7, and 20. Since twins from several countries contributed to the identified loci, an evolutionarily old genetic variant must influence stature in European-based populations. To facilitate the research in the field we have also set up a website that lists all stature genome scans published and their most significant loci (http://www.genomeutwin.org/stature_gene_map.htm).
Objectives To explore the extent to which muscular strength in adolescence is associated with all cause and cause specific premature mortality (<55 years).
Design Prospective cohort study.
Participants 1 142 599 Swedish male adolescents aged 16-19 years were followed over a period of 24 years.
Main outcome measures Baseline examinations included knee extension, handgrip, and elbow flexion strength tests, as well as measures of diastolic and systolic blood pressure and body mass index. Cox regression was used to estimate hazard ratios for mortality according to muscular strength categories (tenths).
Results During a median follow-up period of 24 years, 26 145 participants died. Suicide was a more frequent cause of death in young adulthood (22.3%) than was cardiovascular diseases (7.8%) or cancer (14.9%). High muscular strength in adolescence, as assessed by knee extension and handgrip tests, was associated with a 20-35% lower risk of premature mortality due to any cause or cardiovascular disease, independently of body mass index or blood pressure; no association was observed with mortality due to cancer. Stronger adolescents had a 20-30% lower risk of death from suicide and were 15-65% less likely to have any psychiatric diagnosis (such as schizophrenia and mood disorders). Adolescents in the lowest tenth of muscular strength showed by far the highest risk of mortality for different causes. All cause mortality rates (per 100 000 person years) ranged between 122.3 and 86.9 for the weakest and strongest adolescents; corresponding figures were 9.5 and 5.6 for mortality due to cardiovascular diseases and 24.6 and 16.9 for mortality due to suicide.
Conclusions Low muscular strength in adolescents is an emerging risk factor for major causes of death in young adulthood, such as suicide and cardiovascular diseases. The effect size observed for all cause mortality was equivalent to that for well established risk factors such as elevated body mass index or blood pressure.