Showing papers by "Claude Bouchard published in 2013"

Identification of heart rate–associated loci and their effects on cardiac conduction and rhythm disorders

Abstract: Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

Molecular networks of human muscle adaptation to exercise and age.

Abstract: Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age. Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts. We generated genome-wide transcript profiles from individuals (n = 44) who then undertook 20 weeks of supervised resistance-exercise training (RET). Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%), and when applying Ingenuity Pathway Analysis (IPA) up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR) signaling associating with growth (P = 1.4×10−30). Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs. Differential analysis found networks mimicking developmental processes (activated all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6×10−13) and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = −2.3; P = 3×10−7)) with RET. Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET), they appear to represent “generic” physical activity responsive gene-networks. For age, we found that differential gene-expression methods do not produce consistent molecular differences between young versus old individuals. Instead, utilizing two independent cohorts (n = 45 and n = 52), with a continuum of subject ages (18–78 y), the first reproducible set of age-related transcripts in human muscle was identified. This analysis identified ~500 genes highly enriched in post-transcriptional processes (P = 1×10−6) and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes. The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to the muscle age-related genes. Finally, a number of specific chromosomal loci, including 1q12 and 13q21, contributed by more than chance to the age-related gene list (P = 0.01–0.005), implying possible epigenetic events. We conclude that human muscle age-related molecular processes appear distinct from the processes regulated by those of physical activity.

Can a weight loss of one pound a week be achieved with a 3500-kcal deficit? Commentary on a commonly accepted rule

Abstract: Despite theoretical evidence that the model commonly referred to as the 3500-kcal rule grossly overestimates actual weight loss, widespread application of the 3500-kcal formula continues to appear in textbooks, on respected government- and health-related websites, and scientific research publications. Here we demonstrate the risk of applying the 3500-kcal rule even as a convenient estimate by comparing predicted against actual weight loss in seven weight loss experiments conducted in confinement under total supervision or objectively measured energy intake. We offer three newly developed, downloadable applications housed in Microsoft Excel and Java, which simulates a rigorously validated, dynamic model of weight change. The first two tools available at http://www.pbrc.edu/sswcp, provide a convenient alternative method for providing patients with projected weight loss/gain estimates in response to changes in dietary intake. The second tool, which can be downloaded from the URL http://www.pbrc.edu/mswcp, projects estimated weight loss simultaneously for multiple subjects. This tool was developed to inform weight change experimental design and analysis. While complex dynamic models may not be directly tractable, the newly developed tools offer the opportunity to deliver dynamic model predictions as a convenient and significantly more accurate alternative to the 3500-kcal rule.

Measured maximal heart rates compared to commonly used age-based prediction equations in the heritage family study

Abstract: Objective The purpose of this study was to examine how well two commonly used age-based prediction equations for maximal heart rate (HRmax) estimate the actual HRmax measured in Black and White adults from the HERITAGE Family Study. Methods A total of 762 sedentary subjects (39% Black, 57% Females) from HERITAGE were included. HRmax was measured during maximal exercise tests using cycle ergometers. Age-based HRmax was predicted using the Fox (220-age) and Tanaka (208 – 0.7 × age) formulas. Results The standard error of estimate (SEE) of predicted HRmax was 12.4 and 11.4 bpm for the Fox and Tanaka formulas, respectively, indicating a wide-spread of measured-HRmax values are compared to their age-predicted values. The SEE (shown as Fox/Tanaka) was higher in Blacks (14.4/13.1 bpm) and Males (12.6/11.7 bpm) compared to Whites (11.0/10.2 bpm) and Females (12.3/11.2 bpm) for both formulas. The SEE was higher in subjects above the BMI median (12.8/11.9 bpm) and below the fitness median (13.4/12.4 bpm) when compared to those below the BMI median (12.2/11.0 bpm) and above the fitness median (11.4/10.3) for both formulas. Conclusion Our findings show that based on the SEE, the prevailing age-based estimated HRmax equations do not precisely predict an individual's measured-HRmax. Am. J. Hum. Biol., 25:695–701, 2013. © 2013 Wiley Periodicals, Inc.

Seven to eight hours of sleep a night is associated with a lower prevalence of the metabolic syndrome and reduced overall cardiometabolic risk in adults.

Abstract: Background: Previous studies looking at the relationship between sleep duration and the metabolic syndrome have only used a dichotomous approach (presence/absence) and failed to adjust for important confounding factors. The objective of the present study was to examine the association between self-reported sleep duration and features of the metabolic syndrome in adults. Methods: A cross-sectional analysis from the Quebec Family Study (Canada) was conducted on 810 participants aged 18 to 65 years. Participants were categorized as short (#6 h), adequate (7–8 h) or long ($9 h) sleepers. The metabolic syndrome was defined according to the American Heart Association/National Heart, Lung, and Blood Institute’s criteria. Results: Overall, 24.6% of the sample had the metabolic syndrome. A U-shaped relationship between sleep duration and the prevalence of metabolic syndrome (33.3%, 22.0% and 28.8% in short, adequate and long sleepers, respectively) was observed (P,0.01). Only short sleepers had a significant increase in the odds of having the metabolic syndrome (OR=1.76, 95% CI=1.08–2.84) compared to adequate sleepers after adjustment for age, sex, smoking habits, highest education level, total annual family income, alcohol consumption, coffee intake, menopausal status, daily caloric intake, and moderate-tovigorous physical activity. Likewise, the clustered cardiometabolic risk score (i.e. continuous risk score based on the metabolic syndrome components) was significantly higher in short sleepers compared to adequate sleepers after adjustment for covariates (P,0.05). Conclusion: Sleeping #6 h per night is associated with an elevated cardiometabolic risk score and an increase in the odds of having the metabolic syndrome after adjusting for possible confounders. These results strongly suggest that short sleep duration is a risk factor for the metabolic syndrome.

Advances in exercise, fitness, and performance genomics in 2012.

Abstract: A small number of excellent articles on exercise genomics issues were published in 2012. A new PYGM knock-in mouse model will provide opportunities to investigate the exercise intolerance and very low activity level of people with McArdle disease. New reports on variants in ACTN3 and ACE have increased the level of uncertainty regarding their true role in skeletal muscle metabolism and strength traits. The evidence continues to accumulate on the positive effects of regular physical activity on body mass index or adiposity in individuals at risk of obesity as assessed by their FTO genotype or by the number of risk alleles they carry at multiple obesity-susceptibility loci. The serum levels of triglycerides and the risk of hypertriglyceridemia were shown to be influenced by the interactions between a single nucleotide polymorphism (SNP) in the NOS3 gene and physical activity level. Allelic variation at nine SNPs was shown to account for the heritable component of the changes in submaximal exercise heart rate induced by the HERITAGE Family Study exercise program. SNPs at the RBPMS, YWHAQ, and CREB1 loci were found to be particularly strong predictors of the changes in submaximal exercise heart rate. The 2012 review ends with comments on the importance of relying more on experimental data, the urgency of identifying panels of genomic predictors of the response to regular exercise and particularly of adverse responses, and the exciting opportunities offered by recent advances in our understanding of the global architecture of the human genome as reported by the Encyclopedia of DNA Elements project.

Integrative pathway analysis of a genome-wide association study of V̇o2max response to exercise training

Abstract: We previously reported the findings from a genome-wide association study of the response of maximal oxygen uptake (Vo2max) to an exercise program. Here we follow up on these results to generate hy...

Clinical utility and reproducibility of visceral adipose tissue measurements derived from dual-energy X-ray absorptiometry in white and African American adults

Abstract: Objective The purpose of this study was to determine reproducibility and clinical thresholds for DXA-derived visceral adipose tissue (VAT). Design and Methods The sample included 2317 white and African American adults 18-74 years of age. VAT areas (cm2) were measured using a Hologic DXA scanner equipped with APEX 4.0 software. Reproducibility was assessed using repeated measurements on 101 participants scanned 14 days apart. Receiver Operating Characteristic (ROC) curves were used to assess clinical utility and select thresholds that identified elevated cardiometabolic risk, defined as the presence of ≥2 risk factors. Results Reproducibility of DXA-VAT was 8.1%. The areas under the ROC curves ranged from 0.754 in African American men to 0.807 in white women. The thresholds were higher in white men (154 cm2) and women (143 cm2) compared to African American men (101 cm2) and women (114 cm2). Conclusion The results demonstrated that DXA VAT is a useful clinical marker of cardiometabolic risk; however, further research is required to determine associations with health outcomes using longitudinal studies.

The Importance of Waist Circumference and BMI for Mortality Risk in Diabetic Adults

Abstract: OBJECTIVE We aimed to determine the associations of waist circumference (WC) and BMI with all-cause mortality among patients with diabetes. RESEARCH DESIGN AND METHODS The sample included 847 white and 553 African American patients (18–69 years of age) with diabetes. Height, weight, and WC were measured, and the BMI (kg/m 2 ) was calculated. Cox regression was used to analyze the associations of BMI and WC with mortality, adjusting for age, sex, race, examination year, smoking status, alcohol consumption, and physical activity. Hazard ratios (HRs) are expressed per standard deviation of each independent variable. RESULTS A total of 86 deaths occurred during 6.7 years of follow-up. After adjustment for covariates, WC (HR 1.40 [95% CI 1.14–1.72]) and BMI (1.29 [1.04–1.61]) demonstrated significant relationships with mortality. CONCLUSIONS The results indicate that maintaining a healthy WC and BMI are both important for individuals living with diabetes.

Sedentary behaviour, visceral fat accumulation and cardiometabolic risk in adults: a 6-year longitudinal study from the Quebec Family Study.

Abstract: Background Sedentary behaviour has recently emerged as a unique risk factor for chronic disease morbidity and mortality. One factor that may explain this relationship is visceral adiposity, which is prospectively associated with increased cardiometabolic risk and mortality. The objective of the present study was to determine whether sedentary behaviour was associated with increased accumulation of visceral fat or other deleterious changes in cardiometabolic risk over a 6-year follow-up period among adult participants in the Quebec Family Study.

Abstract P131: Racial Differences in the Response of Cardiorespiratory Fitness to Aerobic Exercise Training in Caucasian and African American Postmenopausal Women

Abstract: Introduction: African American (AA) women have an elevated risk of cardiovascular disease and have been reported to have lower cardiorespiratory fitness compared to Caucasian Americans (CA) women. ...

Anthropometric markers of obesity and mortality in white and African American adults: the pennington center longitudinal study.

Abstract: Objective: The purpose of this study was to determine the association between anthropometric measures of obesity and all-cause mortality in white and African American men and women. Design and Methods: The sample included 14,343 adults 18-89 years of age. Height, weight, and waist and hip circumferences were measured, and the BMI (kg m−2), body adiposity index (BAI = ([hip circumference in centimeters]/[height in meters])1.5 – 18), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR) were computed. Vital status of the participants was determined from linkage with the National Death Index through 2009. Cox regression was used to assess the association between anthropometry and all-cause mortality, adjusting for age, sex, year of baseline examination, study code, smoking status, alcohol consumption and physical activity. Hazard ratios (HR) are expressed per standard deviation of each variable. Results: A total of 438 deaths occurred during 120,637 person-years of follow-up. All anthropometric markers demonstrated significant associations with all-cause mortality in white subjects. In multivariable-adjusted models, BMI (HR 1.34; 95% CI: 1.19-1.50), waist circumference (1.41; 1.25-1.60), BAI (1.34; 1.17-1.53), WHtR (1.46; 1.28-1.65), and WHR (1.40; 1.23-1.61) all demonstrated significant relationships with mortality in white participants, but not in African Americans. In categorical analyses, there was a significant association between BMI status and mortality in whites but not African Americans. However, the risk associated with elevated waist circumference was similar in whites (1.49; 1.15-1.94) and African Americans (1.60; 1.06-2.40). Conclusion: In summary, this study has demonstrated race differences in the association between anthropometry and all-cause mortality.

BMI-specific waist circumference thresholds to discriminate elevated cardiometabolic risk in White and African American adults.

Abstract: Objective: Waist circumference (WC) is a useful anthropometric tool to estimate cardiometabolic risk. However, BMI influences the relationship between WC and health. This study determined BMI-, sex- and race-specific WC thresholds. Methods: The study sample included 6,452 whites and African Americans (AA) aged 18–64 years. WC, BMI, and cardiovascular risk factors were assessed in the clinic. An elevated cardiometabolic risk was defined as the presence of ≥ 2 cardiometabolic risk factors. Receiver Operating Characteristic (ROC) curves were used to determine BMI-, sex-, and race-specific WC thresholds. Results: Based on logistic regression, elevated WC within each BMI category was associated with higher cardiometabolic risk. The respective optimal BMI-specific WC thresholds for white women, AA women, white men, and AA men were as follows: 72, 76, 82, and 78 cm for normal-weight (18.5–24.9 kg/m 2 ); 87, 85, 95, and 92 cm for overweight (25–29.9 kg/m 2 ); 97, 97, 107, and 104 cm for obese I (30–34.9 kg/m 2 ); and 111, 110, 120, and 119 cm for obese II+ ( ≥ 35 kg/m 2 ) participants. Sensitivities ranged from 52.7 to 73.3%, and specificities ranged from 57.1 to 73.5%. Conclusion: The proposed optimal BMI-, sex-, and race-specific WC thresholds are warranted for use in the clinical setting until representative standards become available based on results from longitudinal studies.

Parental eating behavior traits are related to offspring BMI in the Québec Family Study.

Abstract: Parental eating behavior traits have been shown to be related to the adiposity of their young children. It is unknown whether this relationship persists in older offspring or whether rigid or flexible control are involved. The objective of this study was to test the hypothesis that parental eating behavior traits, as measured by the Three-Factor Eating Questionnaire (TFEQ), are related to offspring body weight. Cross-sectional anthropometric and TFEQ data from phase 2 and 3 of the Quebec Family Study generated 192 parent–offspring dyads (offspring age range: 10–37 years). Relationships were adjusted for offspring age, sex and reported physical activity, number of offspring per family and parent body mass index (BMI). In all parent–offspring dyads, parental rigid control and disinhibition scores were positively related to offspring BMI (r=0.17, P=0.02; r=0.18, P<0.01, respectively). There were no significant relationships between cognitive restraint (P=0.75) or flexible control (P=0.06) with offspring BMI. Regression models revealed that parent disinhibition mediated the relationship between parent and offspring BMI, whereas rigid control of the parent moderated this relationship. The interaction effect between parental rigid control and disinhibition was a significant predictor of offspring BMI (β=0.13, P=0.05). Family environmental factors, such as parental eating behavior traits, are related to BMI of older offspring, and should be a focus in the prevention of obesity transmission within families.

The challenging chase for nutrigenetic predictors of metabolic responses to dietary interventions.

Abstract: Development of the metabolic syndrome (MetS) is influenced by genetic and environmental factors. It is of interest to identify genetic factors associated with changes in MetS in response to dietary interventions to maximize the individual benefits gained from preventive or therapeutic measures (i.e., personalized nutrition). In this issue of Diabetes Care , Qi et al. (1) examined the contributions of two genetic variants (rs1522813 and rs2943641) near the insulin receptor substrate 1 ( IRS1 ) gene and their interactions with dietary fat intake on the reversion of the MetS using the data of the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) study. The POUNDS LOST study was a 2-year population-based trial in which 811 overweight and obese adults (64% females) were randomly assigned to one of four diets (2). The percentage of calories derived from the macronutrients varied 20–40% for dietary fat, 15–25% for protein, and 35–65% for carbohydrates. A total of 645 subjects were defined as completers and they lost 4 kg on average with no significant differences among the four dietary groups. MetS was present in 32% of the participants at baseline and this prevalence was reduced to ∼20% at 2 years with no differences between diet groups. Participants changed their diets in the direction of the specified macronutrient goals, but these goals were not fully achieved. For instance, the reported fat intake at 2 years differed from the targets by almost 7 percentage points, with the differences being ∼7% higher for the 20% dietary fat diet group and ∼7% lower for the 40% fat diet group (2). For reasons not specified in the article, Qi et al. used 738 subjects for the current study, a number that apparently includes almost 100 noncompleters as defined in the …

Correction: Molecular Networks of Human Muscle Adaptation to Exercise and Age

Abstract: For the avoidance of any misunderstanding on competing interests, the authors declare that Jamie Timmons is a Founding Director and Thomas Gustafsson, Steen Knudsen and Bethan Phillips are share holders at XR Genomics, a Personalised Health and Fitness company. This should have been indicated at the time of publication. No agreements were in place concerning the execution or publication of this work. The other authors have no competing interests to declare.

composition changes with training in HERITAGE study Uncoupling protein 3 gene is associated with body

Abstract: You might find this additional info useful...This article cites€38 articles, 13 of which you can access for free at: http://jap.physiology.org/content/92/3/1111.full#ref-list-1This article has been cited by€7 other HighWire-hosted articles: http://jap.physiology.org/content/92/3/1111#cited-by Updated information and services including high resolution figures, can be found at: http://jap.physiology.org/content/92/3/1111.fullAdditional material and information about Journal of Applied Physiology can be found at: http://www.the-aps.org/publications/japplThis information is current as of June 5, 2013.

ID polymorphism and elite endurance athlete status No association between the angiotensin-converting enzyme

Abstract: You might find this additional info useful...This article cites€40 articles, 16 of which you can access for free at: http://jap.physiology.org/content/88/5/1571.full#ref-list-1This article has been cited by€20 other HighWire-hosted articles: http://jap.physiology.org/content/88/5/1571#cited-by Updated information and services including high resolution figures, can be found at: http://jap.physiology.org/content/88/5/1571.fullAdditional material and information about Journal of Applied Physiology can be found at: http://www.the-aps.org/publications/japplThis information is current as of June 12, 2013.