Publications

Using a familial correlation model to assess familial influences, baseline dehydroepiandrosterone sulfate (DHEAS) and its change (post-training minus baseline) in response to a 20-week endurance exercise training program were analyzed in 85 black families who participated in the HERITAGE Family Study (HERITAGE). Baseline levels were adjusted for a polynomial in age, and the training response was adjusted for a polynomial in age, as well as the baseline values, within 4 sex-by-generation groups before genetic analysis. We found that the maximal heritability for baseline DHEAS reached 66% (with no sex and generation differences) in black families, which is slightly (but not significantly) higher than the estimate (58%) reported previously in 99 white families in HERITAGE. Whereas weak, but significant, familial effects (26%) for the training response were previously reported for whites in HERITAGE, they were undetectable in the present study. Furthermore, we found heterogeneity in the pattern of familial aggregation (primarily due to different spouse and parent-offspring correlations) for both the baseline and its training response between blacks and whites. In conclusion, baseline DHEAS levels in blacks were also determined by substantial familial factors (just as for whites), independent of the effects of age and sex. Genetic and nongenetic familial components influencing baseline DHEAS levels in both races may be different.

The purpose of this study was to determine the degree of familial resemblance in baseline and 7-year changes in musculoskeletal fitness. Data from the 1981 Canada Fitness Survey and the Campbell's Survey 7-year follow-up were used. The sample consisted of 1264 people (635 males and 629 females) between the ages of 7 and 69 years for whom measurements of musculoskeletal fitness were available at baseline. A subsample of 834 people had measurements at both baseline and 7-year follow-up. Sit-and-reach trunk flexibility, number of push-ups without time limit, number of sit-ups in 60 seconds, and hand-grip strength were used as indicators of musculoskeletal fitness. The data were adjusted for the effects of age and body mass index (and baseline level of the variable for changes) by using regression procedures, and they were standardized to zero mean and unit variance within each of the four sex-by-generation groups (fathers, mothers, sons, and daughters). Familial correlation models were fitted to the data by using the computer software SEGPATH. The results indicate significant familial resemblance for all indicators of musculoskeletal fitness for baseline measures and 7-year changes. The heritabilities, or the percentages of the total variance attributable to heredity, were 64% for trunk flexibility, 37% for push-ups, 59% for sit-ups, and 48% for grip strength. Similarly, heritabilities for the change scores were 48% for trunk flexibility, 52% for push-ups, 41% for sit-ups, and 32% for grip strength. The results suggest that familial, and perhaps genetic, factors are important in explaining the variance in musculoskeletal fitness not only cross-sectionally but also for changes over time.

Objective: To investigate the familial resemblance of 7‐year changes in body mass and adiposity among Canadian families. Research Methods and Procedures: The sample consisted of 655 women and 660 men from 521 families who participated in the Canada Fitness Survey in 1981 and the follow‐up Campbell's Survey in 1988. Indicators of baseline and 7‐year changes in body mass and adiposity included body mass (kilograms), body mass index (BMI; kilograms per square meter), sum of five skinfolds (SF5; millimeters), and waist circumference (WC; millimeters). The data were adjusted for the effects of age and sex, and the change scores were adjusted for baseline levels. A familial correlation model was used to determine the heritability of each phenotype using maximum likelihood techniques. Results: Significant familial resemblance was observed at baseline and for 7‐year changes in all phenotypes. At baseline, moderate heritabilities were observed [body mass: heritability coefficient (h 2 ) = 56%; BMI, h 2 = 39%; SF5, h 2 = 41%; and WC, h 2 = 39%], whereas values were attenuated for each change score except for WC (Δbody mass, h 2 = 23%; ΔBMI, h 2 = 14%; ΔSF5, h 2 = 12%; and ΔWC, h 2 = 45%). Discussion: Changes in body mass and adiposity significantly aggregate within families over 7 years. However, baseline values are characterized by higher heritability levels except WC. The significant heritabilities observed for change scores suggest that lifestyle, transient environmental factors, and possibly age‐related gene effects are important determinants of changes in body mass and adiposity.

This review of the exercise genomics literature emphasizes the strongest articles published in 2010 as defined by sample size, quality of phenotype measurements, quality of the exercise program or physical activity exposure, study design, adjustment for multiple testing, quality of genotyping, and other related study characteristics. One study on voluntary running wheel behavior was performed in 448 mice from 41 inbred strains. Several quantitative trait loci for running distance, speed, and duration were identified. Several studies on the alpha-3 actinin (ACTN3) R577X nonsense polymorphism and the angiotensin-converting enzyme (ACE) I/D polymorphism were reported with no clear evidence for a joint effect, but the studies were generally underpowered. Skeletal muscle RNA abundance at baseline for 29 transcripts and 11 single nucleotide polymorphisms (SNPs) were both found to be predictive of the V˙O2max response to exercise training in one report from multiple laboratories. None of the 50 loci associated with adiposity traits are known to influence physical activity behavior. However, physical activity seems to reduce the obesity-promoting effects of at least 12 of these loci. Evidence continues to be strong for a role of gene-exercise interaction effects on the improvement in insulin sensitivity after exposure to regular exercise. SNPs in the cAMP-responsive element binding position 1 (CREB1) gene were associated with training-induced HR response, in the C-reactive protein (CRP) gene with training-induced changes in left ventricular mass, and in the methylenetetrahydrofolate reductase (MTHFR) gene with carotid stiffness in low-fit individuals. We conclude that progress is being made but that high-quality research designs and replication studies with large sample sizes are urgently needed.

We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. Similar interaction was observed in blacks (P = 0.046). Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals.

KATZMARZYK, PETER T., LOUIS PÉRUSSE, D. C. RAO, AND CLAUDE BOUCHARD. Spousal resemblance and risk of 7‐year increases in obesity and central adiposity in the Canadian population. Obes Res . Objective : Spousal similarities in 7‐year changes in obesity and obesity‐related phenotypes were examined in a sub‐sample of 376 pairs of spouses from a sample of 1487 participants in the 1988 Campbell's Survey follow‐up of the 1981 Canada Fitness Survey. Measures : Indicators of body fatness included the body mass index (BMI), the sum of five skinfolds (SF5), and waist circumference (WAIST), whereas those for relative adipose tissue (AT) distribution included the ratio of two trunk to three extremity skinfolds, adjusted for SF5 (TER adj ), and WAIST adjusted for BMI (WAIST adj ). Results : Spouse correlations were 0. 17, 0. 17, and 0. 17 for the BMI ( p <0. 05) and 0. 20, 0. 20, and 0. 21 for SF5 ( p <0. 05) for the initial measurement, follow‐up, and 7‐year change, respectively. Spouse correlations for WAIST were somewhat lower: 0. 16 ( p <0. 05), 0. 11 ( p <0. 05), and 0. 11 ( p <0. 05) for the initial measurement, follow‐up, and 7‐year change, respectively, whereas those for TER adj and WAIST adj were low and not significant. Spouses of probands who had increases in adiposity and central AT distribution had elevated risks of also increasing in these parameters. Spousal risks (risk ratios) were 1. 48 (95% CI = 1. 08‐2. 03), 1. 49 (95% CI= 1. 10‐2. 02), and 1. 68 (95% CI= 1. 28‐2. 21) for increases in BMI, SF5, and WAIST, respectively, whereas the risks for increases in central adiposity were 1. 22 (95% CI = 0. 86‐1‐73), and 1. 05 (95% CI = 0. 72–153) for TER adj , and WAIST adj , respectively. Discussion : The results indicate significant spousal resemblance and risk for increases in fatness in the general Canadian population, whereas both the spousal resemblance and risks for increases in AT distribution, adjusted for level of fatness, are non‐significant. The results suggest that shared environmental factors may be important determinants of spousal similarities in changes in total body fatness over time; however, cohabitation in the short term may not lead to increases in spousal resemblance.

Shared genetic and familial environmental causes for the associations among resting metabolic rate (RMR), fat‐free mass (FFM), and fat mass (FM) were investigated in families participating in phase 2 of the Québec Family Study. A multivariate familial correlation model assessing the pattern of significant cross‐trait correlations between family members (e.g., RMR in parents with FFM in offspring) was used to infer the etiology of the associations. For each of FM and FFM with RMR, significant sibling, parent‐offspring, and intraindividual cross‐trait correlations suggest the associations are familial. Furthermore, the lack of significant spouse cross‐trait correlations suggests that the familial aggregation is primarily genetic. Bivariate heritability estimates suggest that as much as 45% to 50% of the shared variance between FFM and RMR may be genetic, and as much as 28% to 34% for FM and RMR. This study supports the notion that the gene(s) affecting each of FFM and FM also influence the RMR. Moreover, the lack of any familial associations between FFM and FM suggests that the effects of each body size component on RMR are independent, i.e., more than one genetic source on the RMR‐body size association. The possibility that RMR is an oligogenic trait (i.e., more than one underlying genetic etiology) should be further investigated using more complex multivariate segregation methods until specific genes can be tested.

Several investigations have suggested that body fat distribution is influenced by nonpathologic variations in the responsiveness to Cortisol. Genetic variations in the glucocorticoid receptor (GRL) could therefore potentially have an impact on the level of abdominal fat. A restriction fragment length polymorphism (RFLP) has previously been detected with the Bel I restriction enzyme in the GRL gene identifying two alleles with fragment lengths of 4.5 and 2.3 kb. This study investigates whether abdominal fat areas measured by computerized tomography (CT) are associated with this polymorphism in 152 middle‐aged men and women. The less frequent 4.5‐kb allele was found to be associated with a higher abdominal visceral fat (A VF) area independently of total body fat mass (4.5/4.5 vs. 2.3/2.3 kb genotype; men: 190.7 ± 30.1 vs. 150.7 ± 33.3 cm 2 , p =0.04; women: 132.7 ± 37.3 vs. 101.3 ± 34.5 cm 2 , p =0.06). However, the association with AVF was seen only in subjects of the lower tertile of the percent body fat level. In these subjects, the polymorphism was found to account for 41% ( p =0.003) and 35% ( p =0.007), in men and women, respectively, of the total variance in AVF area. The consistent association between the GRL polymorphism detected with Bel I and AVF area suggests that this gene or a locus in linkage disequilibrium with the Bel I restriction site may contribute to the accumulation of AVF.

Background: There is increasing interest in understanding racial differences in adiposity in specific body depots as a way to explain differential health risks associated with obesity. Objective: Our aim was to examine the differences in abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) between white and African American adults. Design: The sample included 1967 adults aged 18–84 y, including 790 white women, 435 African American women, 606 white men, and 136 African American men. Total body fat was measured by using dual-energy X-ray absorptiometry, whereas abdominal VAT and SAT cross-sectional areas (L4–L5 level) were measured by using computed tomography. Sex-specific differences in SAT and VAT between racial groups were analyzed by the use of general linear models, which controlled for age and total body fat. Additional models tested for racial differences in VAT and SAT and controlled for age, total body fat, smoking, and menopausal status. Statistical significance was accepted at P < 0.05. Results: Abdominal VAT was significantly higher in white than in African American men and women, even after adjustment for covariates. White women had significantly lower SAT than did African American women, both before and after adjustment for covariates. White men had significantly higher SAT than did African American men, but after adjustment for covariates, their SAT was lower than that of African American men. Conclusions: Abdominal visceral adiposity is significantly greater in white men and women. After adjustment for covariates, white men and women had significantly lower SAT than did African American men and women. The results of this study highlight the heterogeneity of human body fat distribution across racial groups.This trial was registered at clinicaltrials.gov as NCT00959270.

Two studies were performed to evaluate the short-term effect of a high-fat diet on spontaneous energy intake and the respective contribution of diet composition and energy density of food. Ingestion of high-fat foods was associated with a significant increase in energy intake in the two studies (P < 0.05). In study 1 this increase was accompanied by a reduction in total weight of food consumed when compared with values obtained under low-fat-diet conditions. Moreover, the occurrence of satiety coincided with a level of carbohydrate intake corresponding to the expected daily carbohydrate oxidation when high-fat foods contained a moderate amount of carbohydrates. In study 2, where the carbohydrate content of high-fat foods was unusually low (≤ 25% of their energy content), carbohydrate intake was lower than usual carbohydrate oxidation. Under the conditions of this study, energy density of foods seemed to play a significant role on the occurrence of satiety.

No abstract is provided for this article.