Genetic Variability of Adult Body Mass Index: A Longitudinal Assessment in Framingham Families

Objective: To explore the contribution of genetics to the mean, SD, maximum value, maximum less the mean, and change over time in body mass index (BMI) and the residual of body weight after adjustment for height. BMI is frequently used as a general indicator of obesity because of its ease and reliability in ascertainment. Cross‐sectional twin and family studies have shown a moderate‐to‐substantial genetic component for BMI. However, the contribution of genetics to the long‐term average, variability, or change over time in BMI is less clear. Research Methods and Procedures: Longitudinal data from the Framingham heart study were used to create pedigrees of age‐matched individuals. Heritability estimates were derived using variance‐decomposition methods on a total of 1051 individuals from 380 extended pedigrees followed for a period of 20 years. All subjects were followed from approximately age 35 to 55 years. Results: Moderate heritability estimates were found for the mean BMI (h² = 0.37), maximum BMI (h² = 0.40), and the mean residual of body weight (h² = 0.36). Low heritability estimates (h² ? 0.20) were found for the maximum less the mean in BMI and the SDs of BMI and residual of body weight. No additive genetic contribution was found for the average change over time in BMI or the residual of body weight. Discussion: These findings suggest that there is a significant genetic component for the magnitude of BMI throughout an individual's middle‐adult years; however, little evidence was found for a genetic contribution to the variability or rate of change in an individual's BMI.     

On the Optimality of F-test on Variance Components in Mixed Linear Models

The analysis-of-variance tests for hypotheses on random effects in regular linear models are considered. Conditions are given for these tests to be uniformly most powerful unbiased or uniformly most powerful invariant unbiased. An example shows that the difference between these conditions can be serious.     

Genetic and Environmental Influences on the Tracking of Body Size from Birth to Early Adulthood

Objective: This study identified genetic and environmental influences on the tracking of body size from birth to 16 to 18.5 years of age. Research Methods and Procedures: Longitudinal information was collected from a nationally representative sample of Finnish twin adolescents (birth cohorts 1975 to 1979) and their parents through questionnaires mailed when the twins were ages 16 and 18.5 years old. The sample included 702 monozygotic, 724 same‐sex dizygotic, and 762 opposite‐sex dizygotic sets of twins. The measures used were length, weight, ponderal index (kilograms per cubic meters), and gestational age at birth, and height, weight, and body mass index (kilograms per square meters) at 16 to 18.5 years of age. The changes in genetic and environmental influences on body size from birth to early adulthood were analyzed by quantitative genetic modeling. Results: The twins who had a higher weight or ponderal index at birth were taller and heavier in early adulthood, whereas those who were longer at birth were taller, but not heavier, later in life. Adult height was affected more by the birth size than body mass index. In the genetic modeling analyses, the genetic factors accounting for the variation of body size became more apparent with age, and both genetic and environmental influences on stature had a sizable carry‐over effect from birth to late adolescence, whereas for relative weight, the influences were more age‐specific. Discussion: The genetic and environmental architecture of body size changes from birth to adulthood. Even in monozygotic twins who share their genetic background, the initially larger twin tended to remain larger, demonstrating the long‐lasting effects of fetal environment on final body size.     

Genetic and Environmental Influences on Body‐Fat Measures among African‐American Twins

Objective: To investigate the genetic and environmental influences on body‐fat measures including waist circumference (WC), waist‐to‐hip ratio (WHR), and body mass index (BMI) among African‐American men and women. Research Methods and Procedures: Measurements were taken as part of the Carolina African American Twin Study of Aging. This sample currently comprises 146 same‐sex African‐American twins with an average age of 50 years (range, 22 to 88 years). This analysis included 26 monozygotic and 29 dizygotic men and 45 monozygotic and 46 dizygotic women. Maximum likelihood quantitative genetic analysis was used. Results: In men, additive genetic effects accounted for 77% of the variance in WC, 59% in WHR, and 89% in BMI. In women, additive genetic effects accounted for 76% of the variance in WC, 56% in WHR, and 73% in BMI. The remaining variance in both men and women was attributed to unique environmental effects (WC, 21%; WHR, 36%; BMI, 11% in men and WC, 22%; WHR, 38%; BMI, 27% in women) and age (WC, 2%; WHR, 5% in men and WC, 2%; WHR, 6% in women). When BMI was controlled in the analysis of WC and WHR, it accounted for a portion of the genetic and environmental variance in WHR and over one‐half of the genetic and environmental variance in WC. Discussion: There are both genetic and environmental influences on WC, WHR, and BMI, and independent of BMI, there are genetic and environmental effects on WC and WHR among both genders. The results from this African‐American twin sample are similar to findings among white twin samples.     

Environmental and genetic influences on body mass and resting metabolic rates (RMR) in a natural population of weasel Mustela nivalis

Body mass (BM) and resting metabolic rates (RMR) are two inexorably linked traits strongly related to mammalian life histories. Yet, there have been no studies attempting to estimate heritable variation and covariation of BM and RMR in natural populations. We used a marker‐based approach to construct a pedigree and then the ‘animal model’ to estimate narrow sense heritability (h²) of these traits in a free‐living population of weasels Mustela nivalis—a small carnivore characterised by a wide range of BM and extremely high RMR. The most important factors affecting BM of weasels were sex and habitat type, whereas RMR was significantly affected only by seasonal variation of this trait. All environmental factors had only small effect on estimates of additive genetic variance of both BM and RMR. The amount of additive genetic variance associated with BM and estimates of heritability were high and significant in males (h² = 0.61), but low and not significant in females (h² = 0.32), probably due to small sample size for the latter sex. The results from the two‐trait model revealed significant phenotypic (r_P = 0.62) and genetic correlation (r_A = 0.89) between BM and whole body RMR. The estimate of heritability of whole body RMR (0.54) and BM corrected RMR (0.45) were lower than estimates of heritability for BM. Both phenotypic and genetic correlations between BM corrected RMR and BM had negative signals (r_P = ?0.42 and r_A = ?0.58). Our results indicate that total energy expenditures of individuals can quickly evolve through concerted changes in BM and RMR.     

Effect of Group vs. Single Housing on Phenotypic Variance in C57BL/6J Mice

Objective: To determine if group housing affects the variance of body composition parameters in a highly inbred mouse strain. Research Methods and Procedures: Thirty 3‐week‐old male C57BL/6J mice were obtained from the Jackson Laboratory. Fifteen mice were housed individually, and 15 mice were housed in groups of 5/cage. Animals were fed ad libitum and maintained in the same room under a 12:12‐hour light/dark photoperiod at 22 °C for 9 weeks. Animals were killed, and fat mass, soft‐lean tissue mass, bone mineral density (BMD), and bone mineral content (BMC) were determined by DXA. At necropsy, weights of the paired epididymal fat pads, paired retroperitoneal fat pads, right inguinal fat pad, liver, kidneys, paired testes, and seminal vesicles were obtained. Results: Relative to mice housed singly, group‐housed mice showed significantly greater variance in percentage of body fat, testes weight, and BMC. Group‐housed mice tended to show greater variance in liver weights and BMD. Mice housed singly were smaller, had less soft‐lean tissue mass and BMC, and lower BMD when compared with group‐housed mice. Discussion: These results suggest that with respect to body composition parameters, mice housed singly are more similar to one another than are group‐housed mice, most likely because of a reduction in environmental (predominately behavioral/social) effects. Thus, mice housed singly may be more representative of genotypic effects on body composition than group‐housed mice. Whether other inbred strains of mice show similar responses to housing condition is unknown.     

Natural selection on the genetical component of variance in body condition in a wild bird population

Although there is substantial evidence that skeletal measures of body size are heritable in wild animal populations, it is frequently assumed that the nonskeletal component of body weight (or ‘condition’) is determined primarily by environmental factors, in particular nutritional state. We tested this assumption by quantifying the genetic and environmental components of variance in fledgling body condition index (=relative body weight) in a natural population of collared flycatchers (Ficedula albicollis), and compared the strength of natural selection on individual breeding values with that on phenotypic values. A mixed model analysis of the components of variance, based on an ‘animal model’ and using 18 years of data on 17 717 nestlings, revealed a significant additive genetic component of variance in body condition, which corresponded to a narrow sense heritability (h²) of 0.30 (SE=0.03). Nongenetic contributions to variation in body condition were large, but there was no evidence of dominance variance nor of contributions from early maternal or common environment effects (pre‐manipulation environment) in condition at fledging. Comparison of pre‐ and post‐selection samples revealed virtually identical h² of body condition index, despite the fact that there was a significant decrease (35%) in the levels of additive genetic variance from fledging to breeding. The similar h² in the two samples occurred because the environmental component of variance was also reduced by selection, suggesting that natural selection was acting on both genotypic and environmental variation. The effects of selection on genetic variance were confirmed by calculation of the selection differentials for both phenotypic values and best linear unbiased predictor (BLUP) estimates of breeding values: there was positive directional selection on condition index both at the phenotypic and the genotypic level. The significant h² of body condition index is consistent with data from human and rodent populations showing significant additive genetic variance in relative body mass and adiposity, but contrasts with the common assumption in ecology that body condition reflects an individual’s nongenetic nutritional state. Furthermore, the substantial reduction in the additive genetic component of variance in body condition index suggests that selection on environmental deviations cannot alone explain the maintenance of additive genetic variation in heritable traits, but that other mechanisms are needed to explain the moderate to high heritabilities of traits under consistent and strong directional selection.     

Meta-Analysis of the Effect of Excluding Early Deaths on the Estimated Relationship between Body Mass Index and Mortality

ALLISON, DAVID B., MYLES S. FAITH, MOONSEONG HEO, DIANA TOWNSEND-BUTTERWORTH, AND DAVID F. WILLIAMSON. Meta-analysis of the effect of excluding early deaths on the estimated relationship between body mass index and mortality. Obes Res. Objectives: Prospective cohort studies typically observe U-or J-shaped relationships between body mass index (BMI) (kg/m²) and mortality. However, some studies suggest that the elevated mortality at lower BMIs is due to confounding by pre-existing occult disease and recommend eliminating subjects who die during the first several (k) years of follow-up. This meta-analysis tests the effects of such early death exclusion on the BMI-mortality association. Research Methods and Procedures: Studies identified from MEDLINE, review articles, ancestry analyses, and the “invisible college.” Included studies: 1) measured relative body weight at baseline; 2) inchded at least 1000 subjects; 3) reported results with and without early-death exclusion, or relevant data; and 4) did not study exclusively diseased populations. Blank tables were mailed to 131 investigators covering 59 databases. Completed tables (n = 16 databases), electronic raw data (n = 7 databases), and original articles (n = 6 databases) provided final data. Meta-analytic regressions compared the BMI-mortality association with and without early death exclusion. The sample included 29 studies and 1,954,345 subjects. Results: The effect of eliminating early deaths was statistically significant but minuscule in magnitude. Implementation of early death exclusion was estimated to shift the BMI associated with minimum mortality only 0. 4 units for men and 0. 6 units for women at age 50. Even at a BMI 16, the estimated relative risk (compared to BMI 25) decreased only 0. 008 units for men and 0. 076 units for women at age 50. Discussion: Results indicate that either pre-existing disease does not confound the BMI—mortality association or eliminating early deaths is inefficient for reducing that confounding.     

Compensatory growth in juvenile roach Rutilus caspicus: effect of starvation and re‐feeding on growth and digestive surface area

The aim of this study was to investigate compensatory growth in juvenile Rutilus caspicus during starvation and re‐feeding periods. The results confirmed the existence of compensatory growth in R. caspicus which depended on the duration of food deprivation. Complete compensatory growth occurred in the fish that were food deprived for at least 3 weeks. Starvation and re‐feeding had no significant effect on the digestive somatic index and intestinal surface areas in the fish that were food deprived for 1 week, while they showed a significant decrease and increase, during starvation and re‐feeding in the fish that were food deprived for 2 and 3 weeks. This knowledge may have application in aquaculture, as appropriate exploitation of compensatory growth can give increased growth rate and feeding efficiency.     

The Fat-Sucrose Seesaw in Relation to Age and Dietary Variety of French Adults

DREWNOWSKI, ADAM, SUSAN AHLSTROM HENDERSON, AMY BETH SHORE, CLAUDE FISCHLER, PAUL PREZIOSI, SERGE HERCBERG. The fatsucrose seesaw in relation to age and dietary variety of French adults. Guidelines for a healthy diet often recommend limiting dietary sugars and fats. Some researchers have called these aims mutually incompatible, suggesting that fat and sugar intakes, when expressed as percent dietary energy, are inversely linked. Others have argued that sugar, more specifically sucrose, acts as a vehicle for dietary fat and serves to suppress the overall quality of the diet. This study examined the relationship between age, sucrose and fat intakes, body mass index (BMI), and measures of dietary diversity and variety in a communitybased sample of 837 French adults. Consistent with other studies, high consumption of added sucrose (in g/day or g/1000 kcal per day) was associated with higher consumption of energy and fat and lower consumption of vegetables and fruit. However, eating patterns were strongly influenced by age. High-sucrose consumers were significantly younger and had lower BMI values than did low-sucrose consumers, who were both older and had higher BMIs. High-sucrose diets had minimal effect on the diet diversity score and were associated with more varied diets, as evidenced by a higher dietary variety score.     

Evaluation of the Best Linear Unbiased Prediction in Mixed Linear Models with Estimated Variance Components by Means of the MSE of Prediction and the Genetic Selection Differential

Prediction in mixed linear models by Henderson 's (1972) BLUP (Best Linear Unbiased Prediction) requires knowledge of the underlying variance/covariance components to have the property ‘best’. In breeding value prediction these parameters are not known, generally. They have to be replaced by estimations and BLUP becomes estimated BLUP (EBLUP). The aim of this investigation was the evaluation of EBLUP with help of a designed simulation experiment. Criteria used for the evaluation were the mean squared error (MSE) and the (genetic) selection differential (GSD). Besides, an idea of the overestimation of the accuracy of EBLUP by the naive MSE approximation based on the MSE formulas of BLUP with variance component estimations instead of unknown parameters is given.     

Effect of Smoking on the Paradox of High Waist‐to‐Hip Ratio and Low Body Mass Index

Objective: Research on diabetes mellitus (DM) indicates that people with a low body mass index (BMI) but a high waist‐to‐hip ratio (WHR) are in a particularly high‐risk group. The purpose of this study was to investigate the prevalence of and the effect of smoking on this paradoxical relationship. Research Methods and Procedures: Our study sample consisted of 3450 men and 4250 women who had participated in the Korean Nationwide Health Examination Survey. We divided the study sample into tertiles (low, medium, and high), according to the level of WHR and of BMI, which yielded nine different combinations. Individuals exhibiting so‐called paradox A had the highest WHR and the lowest BMI. Results: The prevalence of paradox A was 4.7% for men and 3.8% for women. The overall agreement of WHR and BMI groups was poor [for men: κ = 0.31 and 95% confidence interval (CI) = 0.29 to 0.34; for women: κ = 0.39 and 95% CI = 0.37 to 0.42 for women]. The odds ratios for subjects having paradox A were estimated using a logistic regression model after adjusting for age, age², height, education, smoking, use of alcohol, and exercise. The risk for paradox A among current smokers was 2.1‐fold (95% CI, 1.5 to 3.0) higher for men and 2.5‐fold (95% CI, 1.6 to 3.9) higher for women than for nonsmokers, after adjusting for age and covariates. Discussion: Cigarette smoking may increase the risk of paradox A. The findings of this study should be crossvalidated to different populations.     

Effect of Dominance,Reproductive State,and Group Size on Body Mass in Macaca radiata

Body mass can impact reproductive performance in males and females. In nonhuman primates the relationship is often mediated by dominance. We measured body mass monthly in a provisioned group of bonnet macaques (Macaca radiata) living at a Hindu temple. We also measured body mass on 3 occasions in a wild population of bonnet macaques. In the temple group, females that reproduced lost body mass, while females that did not reproduce gained body mass. Mass loss among females occurred primarily while they were nursing. Adult males from the temple group lost mass during the mating season and gained it during the non-mating season. Subadult males experienced less seasonal variation in body mass. Body mass and changes in mass were not related to dominance rank in either the temple or the forest group. Furthermore, maternal dominance rank did not affect infant mass. Females from the smallest forest group weighed significantly less than females from the two larger forest groups, which suggests intergroup competition in the population. Body mass was not related to dominance rank in a straightforward manner but may indirectly affect reproductive performance. The pattern of body mass change suggests that the period of lactation is critical for females and endurance rivalry is an important form of competition among males.     

Distribution of Anthropometric Variables and the Prevalence of Obesity in Populations of West African Origin: The International Collaborative Study on Hypertension in Blacks (ICSHIB)

A survey of the prevalence of hypertension and associated risk factors including obesity was carried out among persons of West African heritage currently living in societies at different stages of social, economic and technological development. We present here the distribution of several anthropometric variables and the prevalence of obesity in these populations. Using a standard protocol with centralized training of field staff, 7 439 men and women aged 24 to 75 from six multinational sites were recruited and examined. Although men were taller, women were more obese across sites. Body mass index (BMI) and consequently the prevalence of overweight and obesity increased with westernization from rural African subsistence farming communities to suburban Chicago. Average BMI increased with age until about age 54, and then began to decline or at least level off. The mean BMI for African-American men and women was 27.1 kg/m² and 30.8 kg/m², respectively. Men displayed high levels of centripetal fatness, measured as the waist-to-hip ratio (WHR), compared to the women across site. Based on the US Department of Agriculture guidelines, 22.6% and 56.9% of the African-American men and women had elevated WHR. Although account must be taken of the important contribution of an individual's genetic background, this multinational study of persons with similar heritage clearly shows the potent impact of current environmental factors on the distribution and level of obesity.     

Effects of temperature on prey consumption and growth in mass of juvenile trahira Hoplias aff. malabaricus (Bloch, 1794)

The influence of temperature on prey consumption and growth in mass of juvenile trahira Hoplias aff. malabaricus were investigated. Consumption of small-sized lambari Astyanax altiparanae (mean standard length, L _S, 5·43 cm) varied from zero to 65 over a period of 30 days. Temperatures ranged from 14 to 34° C and the size of trahiras ranged from 17·5 to 24·7 cm L _S. Prey consumption differed significantly among temperatures. Trahiras at 18° C consumed significantly less than those at 30° C. A linear multiple regression model including temperature, prey consumption and L _S explained 89·4% of the variability in growth in mass. Some caution is suggested when inferring the impact of H. aff. malabaricus piscivory on assemblage structures in systems that, despite their location in tropical regions, are subjected to seasonal thermal variations.     

Influence of confounding factors on plasma Mid-Regional pro-Adrenomedullin and Mid-Regional pro-A-type Natriuretic Peptide concentrations in healthy individuals

Background: MRproADM and MRproANP can be used as diagnostic and prognostic markers in heart failure.

Aim: The objective was to identify confounding factors for the interpretation of plasma MRproADM and MRproANP concentrations.

Methods: A total of 518 healthy volunteers with a mean age of 60.84?±?7.41 years were analyzed. We evaluated the influence of demographic factors, renal function and echocardiographic indices on the candidate peptides.

Results: Multivariate analysis revealed that age (P?<?0.001), BMI (P?<?0.001) and eGFR (P?<?0.001) were independent predictors for MRproADM concentrations in healthy subjects. The independent predictors for MRproANP were age (P?<?0.001), female gender (P?<?0.001), heart rate (P?<?0.001) and eGFR (P?=?0.039).

Conclusion: The interpretation of both peptides is multifaceted due to confounders. Knowledge of these factors will further our understanding of how these peptides behave in health and in disease.