Karri Silventoinen

Heritability of Adult Body Height: A Comparative Study of Twin Cohorts in Eight Countries

A major component of variation in body height is due to genetic differences, but environmental factors have a substantial contributory effect. In this study we aimed to analyse whether the genetic architecture of body height varies between affluent western societies. We analysed twin data from eight countries comprising 30,111 complete twin pairs by using the univariate genetic model of the Mx statistical package. Body height and zygosity were self-reported in seven populations and measured directly in one population. We found that there was substantial variation in mean body height between countries; body height was least in Italy (177 cm in men and 163 cm in women) and greatest in the Netherlands (184 cm and 171 cm, respectively). In men there was no corresponding variation in heritability of body height, heritability estimates ranging from 0.87 to 0.93 in populations under an additive genes/unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well or better, heritability ranged from 0.89 to 0.93. This difference between the sexes was mainly due to the effect of the shared environmental component of variance, which appears to be more important among women than among men in our study populations. Our results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men.

DETERMINANTS OF VARIATION IN ADULT BODY HEIGHT

Final body height is achieved as the result of a combination of genetic and environmental factors. The aim of this article is to review past studies on body height that have followed different scientific traditions. In modern Western societies, about 20% of variation in body height is due to environmental variation. In poorer environments, this proportion is probably larger, with lower heritability of body height as well as larger socioeconomic body height differences. The role of childhood environment is seen in the increase in body height during the 20th century simultaneously with the increase in the standard of living. The most important non-genetic factors affecting growth and adult body height are nutrition and diseases. Short stature is associated with poorer education and lower social position in adulthood. This is mainly due to family background, but other environmental factors in childhood also contribute to this association. Body height is a good indicator of childhood living conditions, not only in developing countries but also in modern Western societies. Future studies combining different scientific traditions in auxology are needed to create a more holistic view of body height.

The effects of physical activity and body mass index on cardiovascular, cancer and all-cause mortality among 47 212 middle-aged Finnish men and women.

OBJECTIVE:To examine the association of physical activity and body mass index (BMI), and their combined effect, with the risk of total, cardiovascular disease (CVD) and cancer mortality.DESIGN:Prospective follow-up study.SUBJECTS:In all, 22 528 men and 24 684 women aged 25–64 y at baseline having 7394 deaths during a mean follow-up of 17.7 y.MEASUREMENT:A self-administered questionnaire data on smoking, socioeconomic factors, physical activity and medical history, together with measured height, weight, blood pressure and serum cholesterol using standardized protocol.RESULT:Physically active subjects had significantly lower age-adjusted mortality from cardiovascular, cancer and all causes compared with sedentary ones. Further adjustment for smoking, systolic blood pressure, cholesterol, BMI, diabetes and education affected the results only slightly. Obese subjects (BMI≥30 kg/m2) had significantly higher cardiovascular and total mortality than the normal weight (18.5≤BMI<25 kg/m2) subjects. Part of increased mortality among obese subjects was mediated through obesity-related cardiovascular risk factors. BMI had an inverse association with cancer mortality among men and almost significant direct association among women. Total mortality was also increased among the lean (BMI<18.5 kg/m2) subjects. However, less than 0.3% of deaths were attributed to low body weight, whereas in men 5.5% and in women 17.7% of deaths were attributed to obesity.CONCLUSION:Regular physical activity and normal weight are both important indicators for a decreased risk of mortality from all causes, CVD and cancer. Physical activity had a strong independent effect on mortality, whereas the effect of BMI was partly mediated through other obesity-related risk factors.

The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies

In this systematic review, we aimed to collect together all previous twin and adoption studies on childhood and adolescent obesity up to the age of 18 years. Using several sources, we identified nine twin and five adoption studies; all of these studies had used relative weight as an indicator of obesity. Except the two twin studies from the Korean population, all studies represented Caucasian populations. In a meta-analysis of these twin studies, we found that genetic factors had a strong effect on the variation of body mass index (BMI) at all ages. The common environmental factors showed a substantial effect in mid-childhood, but this effect disappeared at adolescence. Adoption studies supported the role of family environment in childhood obesity as correlations were found between adoptees and adoptive parents; however, correlations were substantially stronger between parents and their biological offspring, further supporting the importance of genetic factors. In the future, more studies implementing genetic and environmental measures into twin models are needed as they allow estimation of the proportion of total genetic variation explained by candidate genes and analyses of gene–environment interactions. More studies of genetic architecture in non-Caucasian populations, of gene–environment interactions, and of body composition and body fat distribution are needed.

Emotional eating, depressive symptoms and self-reported food consumption. A population-based study.

We examined the associations of emotional eating and depressive symptoms with the consumption of sweet and non-sweet energy-dense foods and vegetables/fruit, also focusing on the possible interplay between emotional eating and depressive symptoms. The participants were 25-64-year-old Finnish men (n=1679) and women (n=2035) from the FINRISK 2007 Study (DILGOM substudy). The Three-Factor Eating Questionnaire-R18, Center for Epidemiological Studies Depression Scale, and a 132-item Food Frequency Questionnaire were used. Emotional eating and depressive symptoms correlated positively (r=0.31 among men and women), and both were related to a higher body mass. Emotional eating was related to a higher consumption of sweet foods in both genders and non-sweet foods in men independently of depressive symptoms and restrained eating. The positive associations of depressive symptoms with sweet foods became non-significant after adjustment for emotional eating, but this was not the case for non-sweet foods. Depressive symptoms, but not emotional eating, were related to a lower consumption of vegetables/fruit. These findings suggest that emotional eating and depressive symptoms both affect unhealthy food choices. Emotional eating could be one factor explaining the association between depressive symptoms and consumption of sweet foods, while other factors may be more important with respect to non-sweet foods and vegetables/fruit.

Leisure Time, Occupational, and Commuting Physical Activity and the Risk of Stroke

Background and Purpose— The role of physical activity, especially that of occupational and commuting physical activity, in the prediction of stroke risk is not properly established. We assessed the relationship of different types of physical activity with total and type-specific stroke risk. Methods— We prospectively followed 47 721 Finnish subjects 25 to 64 years of age without a history of coronary heart disease, stroke, or cancer at baseline. Hazard ratios (HRs) for incident stroke were estimated for different levels of leisure time, occupational, and commuting physical activity. Results— During a mean follow-up of 19.0 years, 2863 incident stroke events were ascertained. The multivariate-adjusted (age, sex, area, study year, body mass index, systolic blood pressure, cholesterol, education, smoking, alcohol consumption, diabetes, and other 2 types of physical activity) HRs associated with low, moderate, and high leisure time physical activity were 1.00, 0.86, and 0.74 (Ptrend<0.001) for total stroke, 1.00, 0.87, and 0.46 (Ptrend=0.011) for subarachnoid hemorrhage, 1.00, 0.77, and 0.63 (Ptrend=0.024) for intracerebral hemorrhage, and 1.00, 0.87, and 0.80 (Ptrend=0.001) for ischemic stroke, respectively. The multivariate-adjusted HRs associated with none, 1 to 29, and ≥30 minutes of active commuting were 1.00, 0.92, and 0.89 (Ptrend=0.043) for total stroke, and 1.00, 0.93, and 0.86 (Ptrend=0.028) for ischemic stroke, respectively. Occupational activity had a modest association with ischemic stroke in the multivariate analysis (Ptrend=0.046). Conclusion— A high level of leisure time physical activity reduces the risk of all subtypes of stroke. Daily active commuting also reduces the risk of ischemic stroke.

Muscular strength in male adolescents and premature death: cohort study of one million participants

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. Setting Sweden. 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.

Combined Genome Scans for Body Stature in 6,602 European Twins: Evidence for Common Caucasian Loci

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).

Physical activity reduces the influence of genetic effects on BMI and waist circumference: a study in young adult twins

Objective:Both obesity and exercise behavior are influenced by genetic and environmental factors. However, whether obesity and physical inactivity share the same genetic vs environmental etiology has rarely been studied. We therefore analyzed these complex relationships, and also examined whether physical activity modifies the degree of genetic influence on body mass index (BMI) and waist circumference (WC).Methods:The FinnTwin16 Study is a population-based, longitudinal study of five consecutive birth cohorts (1975–1979) of Finnish twins. Data on height, weight, WC and physical activity of 4343 subjects at the average age of 25 (range, 22–27 years) years were obtained by a questionnaire and self-measurement of WC. Quantitative genetic analyses based on linear structural equations were carried out by the Mx statistical package. The modifying effect of physical activity on genetic and environmental influences was analyzed using gene-environment interaction models.Results:The overall heritability estimates were 79% in males and 78% in females for BMI, 56 and 71% for WC and 55 and 54% for physical activity, respectively. There was an inverse relationship between physical activity and WC in males (r=−0.12) and females (r=−0.18), and between physical activity and BMI in females (r=−0.12). Physical activity significantly modified the heritability of BMI and WC, with a high level of physical activity decreasing the additive genetic component in BMI and WC.Conclusions:Physically active subjects were leaner than sedentary ones, and physical activity reduced the influence of genetic factors to develop high BMI and WC. This suggests that the individuals at greatest genetic risk for obesity would benefit the most from physical activity.

Heritability of body size and muscle strength in young adulthood: a study of one million Swedish men

Moderate heritability for skeletal muscle strength has been reported in twin studies, but genetic co‐variation between muscle strength at different parts of body and body size is not well known. Further, representativeness of twin cohorts needs to be critically evaluated. Height, weight, elbow flexion, hand grip and knee extension strength were measured in young adulthood in 1,139,963 Swedish men born between 1951 and 1976. We identified 154,970 full‐brother pairs and 1582 monozygotic (MZ) and 1864 same‐sex dizygotic (DZ) complete twin pairs. The data were analyzed using quantitative genetic modeling for twin and family data. Twins compared to singletons and MZ twins compared to DZ twins were shorter, lighter and had lower muscle strength. In singletons, there was more variation in weight and the strength measures compared to twins with known zygosity but not when compared to twins with unknown zygosity. Full‐sib correlations for these traits were lower than DZ correlations. Additive genetic factors explained 81% of variation in height, 59% in body mass index and 50–60% in the strength measures. Additive genetic correlations varied from 0.13 between height and elbow flexion strength to 0.78 between elbow flexion and hand grip strength. Our results suggest that extra variation may exist in general populations not found in twin samples, probably because of selection due to non‐participation. This may have inflated heritability estimates in previous twin studies. Nonetheless, we showed that genetic factors affect muscle strength and part of these genes are common to different strength indicators and body size. Genet. Epidemiol.