Showing papers by "Claude Bouchard published in 2010"

Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans.

Abstract: A low maximal oxygen consumption (Vo2max) is a strong risk factor for premature mortality. Supervised endurance exercise training increases Vo2max with a very wide range of effectiveness in human...

Advances in exercise, fitness, and performance genomics.

Abstract: An annual review publication of the most significant articles in exercise, fitness, and performance genomics begins with this article, which covers 2 yr, 2008 and 2009. The review emphasizes the strongest articles 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. With this avowed focus on the highest quality articles, only a small number of published articles are reviewed. Among the most significant findings reported here are a brief overview of the first genome-wide association study of the genetic differences between exercisers and nonexercisers. In addition, the latest results on the actinin alpha 3 (ACTN3) R577X nonsense polymorphism are reviewed, emphasizing that no definitive conclusion can be reached at this time. Recent studies that have dealt with mitochondrial DNA haplogroups and endurance performance are described. Published reports indicating that physical activity may attenuate the effect of the fat mass and obesity associated (FTO) gene risk allele on body mass index are reviewed. Articles that have tested the contributions of specific genes to the response of glucose and insulin metabolism traits to regular exercise or physical activity level are considered and found to be generally inconclusive at this stage. Studies examining ethnic differences in the response of blood lipids and lipoproteins to exercise training cannot unequivocally relate these to apolipoprotein E (APOE) genotypes. Hemodynamic changes with exercise training were reported to be associated to sequence variation in kinesin heavy chain (KIF5B), but no replication study is available as of yet. We conclude from this first installment that exercise scientists need to prioritize high-quality research designs and that replication studies with large sample sizes are urgently needed.

Maintaining a high physical activity level over 20 years and weight gain.

Abstract: Context Data supporting physical activity guidelines to prevent long-term weight gain are sparse, particularly during the period when the highest risk of weight gain occurs. Objective To evaluate the relationship between habitual activity levels and changes in body mass index (BMI) and waist circumference over 20 years. Design, Setting, and Participants The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective longitudinal study with 20 years of follow-up, 1985-1986 to 2005-2006. Habitual activity was defined as maintaining high, moderate, and low activity levels based on sex-specific tertiles of activity scores at baseline. Participants comprised a population-based multicenter cohort (Chicago, Illinois; Birmingham, Alabama; Minneapolis, Minnesota; and Oakland, California) of 3554 men and women aged 18 to 30 years at baseline. Main Outcome Measures Average annual changes in BMI and waist circumference. Results Over 20 years, maintaining high levels of activity was associated with smaller gains in BMI and waist circumference compared with low activity levels after adjustment for race, baseline BMI, age, education, cigarette smoking status, alcohol use, and energy intake. Men maintaining high activity gained 2.6 fewer kilograms (+0.15 BMI units per year; 95% confidence interval [CI], 0.11-0.18 vs +0.20 in the lower activity group; 95% CI, 0.17-0.23), and women maintaining higher activity gained 6.1 fewer kilograms (+0.17 BMI units per year; 95% CI, 0.12-0.21 vs +0.30 in the lower activity group; 95% CI, 0.25-0.34). Men maintaining high activity gained 3.1 fewer centimeters in waist circumference (+0.52 cm per year; 95% CI, 0.43-0.61 cm vs 0.67 cm in the lower activity group; 95% CI, 0.60-0.75 cm) and women maintaining higher activity gained 3.8 fewer centimeters (+0.49 cm per year; 95% CI, 0.39-0.58 cm vs 0.67 cm in the lower activity group; 95% CI, 0.60-0.75 cm). Conclusion Maintaining high activity levels through young adulthood may lessen weight gain as young adults transition to middle age, particularly in women.

The Pediatric Obesity Epidemic Continues Unabated in Bogalusa, Louisiana

Abstract: OBJECTIVES: To examine 35-year trends in the prevalence of overweight and obesity among children and adolescents from Bogalusa, Louisiana. PATIENTS AND METHODS: Height and weight were measured for 11653 children and adolescents between 5 and 17 years of age in 8 cross-sectional surveys. The Bogalusa Heart Study contributed data from 1973–1994, and routine school screening provided 2008–2009 data. Trends in mean BMI, mean gender-specific BMI-for-age z scores, prevalence of overweight/obesity (BMI ≥ 85th percentile), and prevalence of obesity (BMI ≥ 95th percentile) according to age, race, and gender were examined. RESULTS: Since 1973–1974, the proportion of children and adolescents aged 5 to 17 years who are overweight (overweight plus obese) has more than tripled, from 14.2% to 48.4% in 2008–2009. Similarly, the proportion of obese children and adolescents has increased more than fivefold from 5.6% in 1973–1974 to 30.8% in 2008–2009. The prevalence of overweight or obesity, and secular changes, were similar among black and white boys and girls. CONCLUSIONS: In semirural Bogalusa, the childhood obesity epidemic has not plateaued, and nearly half of the children are now overweight or obese.

Improvements in glucose homeostasis in response to regular exercise are influenced by the PPARG Pro12Ala variant: results from the HERITAGE Family Study.

Abstract: Aims/hypothesis Exercise training improves glucose homeostasis, but large inter-individual differences are reported, suggesting a role of genetic factors. We investigated whether variants either confirmed or newly identified as diabetes susceptibility variants through genome-wide association studies (GWAS) modulate changes in phenotypes derived from an IVGTT in response to an endurance training programme.

Risk factors for adult overweight and obesity: the importance of looking beyond the 'big two'.

Abstract: Objective: To compare two traditional (high dietary lipid intake and non-participation in high-intensity physical exercise, namely the ‘Big Two’ factors) versus three nontraditional (short sleep duration, high disinhibition eating behavior, and low dietary calcium intake) risk factors as predictors of excess body weight and overweight/obesity development Method: Adult participants aged 18–64 years of the Quebec Family Study were selected for cross-sectional (n = 537) and longitudinal (n = 283; 6-year follow-up period) analyses The main outcome measure was overweight/obesity, defined as a BMI ≧ 25 kg/m2 Results: We observed that both the prevalence and incidence of overweight/obesity was best predicted by a combination of risk factors However, short sleep duration, high disinhibition eating behavior and low dietary calcium intake seemed to contribute more to the risk of overweight and obesity than high dietary lipid intake and non-participation in high-intensity physical exercise Globally, the risk of being overweight or obese was two-fold higher for individuals having the three nontraditional risk factors combined (OR 605; 95% CI 426–788) compared to those reporting a high percentage of lipids in their diet together with no vigorous physical activity in their daily schedule (OR 295; 95% CI 218–373) Furthermore, the risk of overweight/obesity was also higher for the combination of any two of the nontraditional risk factors than for the combination of the ‘Big Two’ factors Conclusion: These results are concordant with previous reports showing that obesity is a multifactorial condition, and emphasize the importance of looking beyond reported measures of the ‘Big Two’ factors

The Three-Factor Eating Questionnaire and BMI in adolescents: results from the Quebec Family Study

Abstract: Eating behaviour traits are associated with body weight variations in adults. The Three-Factor Eating Questionnaire (TFEQ) measures cognitive restraint, disinhibition and hunger, as well as their corresponding subscales, e.g. rigid and flexible control. The TFEQ has not been widely used in adolescents to investigate eating behaviour traits associated with body weight. The aim of the present study was to assess whether eating behaviour traits were associated with BMI in male and female adolescents. Sixty adolescents (thirty females and thirty males; mean age 15.0 (sd 2.4) years) from the Quebec Family Study completed the TFEQ and 3 d dietary records. There were no sex differences in the TFEQ scores. Rigid control, disinhibition and emotional susceptibility (to overeat) were positively related to BMI z-scores for the entire sample (r 0.3, P < 0.05). There was a positive relationship between BMI z-scores and rigid control (r 0.39, P < 0.05) in females, while BMI z-scores were positively related to emotional susceptibility (r 0.42, P < 0.02) and disinhibition (r 0.41, P < 0.03) in males. Adolescents characterised by both high disinhibition and high rigid control had significantly higher BMI z-scores than those by both low disinhibition and low rigid control. There were no significant differences in BMI z-scores between the flexible control categories. Dietary macronutrient content was not consistently related to eating behaviour traits. These results show that the eating behaviour traits of disinhibition and rigid control are independently related to BMI z-scores in this group of adolescents.

FTO genotype is associated with exercise training-induced changes in body composition

Abstract: The fat mass (FM) and obesity-associated (FTO) gene is the first obesity-susceptibility gene identified by genome-wide association scans and confirmed in several follow-up studies. Homozygotes for the risk allele (A/A) have 1.67 times greater risk of obesity than those who do not have the allele. However, it is not known whether regular exercise-induced changes in body composition are influenced by the FTO genotype. The purpose of our study was to test whether the FTO genotype is associated with exercise-induced changes in adiposity. Body composition was derived from underwater weighing before and after a 20-week endurance training program in 481 previously sedentary white subjects of the HERITAGE Family Study. FTO single-nucleotide polymorphism (SNP) rs8050136 was genotyped using Illumina GoldenGate assay. In the sedentary state, the A/A homozygotes were significantly heavier and fatter than the heterozygotes and the C/C homozygotes in men (P = 0.004) but not in women (P = 0.331; gene-by-sex interaction P = 0.0053). The FTO genotype was associated with body fat responses to regular exercise (P < 0.005; adjusted for age, sex, and baseline value of response trait): carriers of the C allele showed three times greater FM and %body fat losses than the A/A homozygotes. The FTO genotype explained 2% of the variance in adiposity changes. Our data suggest that the FTO obesity-susceptibility genotype influences the body fat responses to regular exercise. Resistance to exercise-induced reduction in total adiposity may represent one mechanism by which the FTO A allele promotes overweight and obesity.

A common haplotype and the Pro582Ser polymorphism of the hypoxia-inducible factor-1alpha (HIF1A) gene in elite endurance athletes.

Abstract: Hypoxia-inducible factor-1alpha (HIF1A) is a transcription factor regulating several genes in response to hypoxic stimuli. HIF1A target genes code for proteins involved in oxygen transport, glycolytic enzymes, and glucose transporters. We investigated whether single-nucleotide polymorphisms and haplotypes in the HIF1A gene are associated with endurance performance in the Genathlete cohort, which includes 316 Caucasian male elite endurance athletes (EEA) with a maximal oxygen uptake of 79.0+/-3.5 ml.kg(-1).min(-1) (mean+/-SD) and 304 Caucasian male sedentary controls with a maximal oxygen uptake of 40.1+/-7.0 ml.kg(-1).min(-1). Six single-nucleotide polymorphisms (rs1951795, rs11158358, rs2301113, rs11549465, rs115494657, rs17099207) were genotyped with the TaqMan system. We found a nominal significant tendency for a difference between the two groups for HIF1A Pro582Ser (rs11549465) genotype distributions (Pchi2=0.017). Homozygotes of the Pro genotype were slightly more frequent in athletes than in controls (84 vs. 75%). Compared with Ser carriers, the odds ratio (OR) of being an EEA in Pro/Pro homozygotes was 1.77 [95% confidence interval (CI): 1.18-2.67, P=0.006] compared with the other genotypes. A common HIF1A haplotype (frequency: 15%), including the rs11549465 Pro allele and the minor A allele of rs17099207 in the 3' flanking region of the gene, showed a significant association with EEA status (OR: 2.37, 95% CI: 1.21-4.66, P=0.012), whereas the most prevalent haplotype (frequency: 59%) comprising the rs11549465 Pro allele and the major G allele of rs1709920 showed no association with EEA status (OR: 0.93, 95% CI: 0.58-1.50, P=0.769). We found preliminary evidence that the HIF1A Pro582Ser polymorphism and a common haplotype of the HIF1A gene may be associated with EEA status in Caucasian men.

ACTN3 R577X and other polymorphisms are not associated with elite endurance athlete status in the Genathlete study.

Abstract: Homozygosity for a premature stop codon at amino acid position 577 in the alpha-actinin-3 (ACTN3) gene leads to α-actinin-3 deficiency. This genotype is observed in approximately 18% of Caucasians. The ACTN3 R577X polymorphism has been previously associated with indicators of physical performance in several, but not all, studies. We examined the prevalence of R577X (rs1815739) and two additional haplotype tagging single nucleotide polymorphisms (htSNPs) of the ACTN3 gene (rs1791690 and rs2275998) in the Genathlete study comprising 316 male elite endurance athletes ([Vdot]O2max 79.0 ± 3.5 ml · kg−1 · min−1; mean ± s) from North America, Finland, and Germany and 304 sedentary controls ([Vdot]O2max 40.1 ± 7.0 ml · kg−1 · min−1) matched by country of origin. The distribution of genotype and allele frequencies between the two groups was tested by Pearson chi-square and/or Fischer exact test. The prevalence of the 577X homozygote genotype was similar in endurance athletes and controls (20% and 17.5%, r...

Longitudinal examination of age-predicted symptom-limited exercise maximum HR.

Abstract: Purpose:To estimate the association of age with maximal HR (MHR).Methods:Data were obtained from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants were black and white men and women aged 18-30 yr in 1985-1986 (year 0). A symptom-limited maximal graded exercise

CREB1 Is a Strong Genetic Predictor of the Variation in Exercise Heart Rate Response to Regular Exercise: The HERITAGE Family Study

Abstract: Background— A genome-wide linkage scan identified a quantitative trait locus for exercise training–induced changes in submaximal exercise (50 W) heart rate (ΔHR50) on chromosome 2q33.3-q34 in the HERITAGE Family Study (n=472). Methods and Results— To fine-map the region, 1450 tag SNPs were genotyped between 205 and 215 Mb on chromosome 2. The strongest evidence of association with ΔHR50 was observed with 2 single-nucleotide polymorphisms (SNPs) located in the 5′ region of the cAMP-responsive element-binding protein 1 ( CREB1 ) gene (rs2253206: P =1.6×10 −5 and rs2360969: P =4.3×10 −5 ). The associations remained significant ( P =0.01 and P =0.023, respectively) after accounting for multiple testing. Regression modeling of the 39 most significant SNPs in the single-SNP analysis identified 9 SNPs that collectively explained 20% of the ΔHR50 variance. CREB1 SNP rs2253206 had the strongest effect (5.45% of variance), followed by SNPs in the FASTKD2 (3.1%), MAP2 (2.6%), SPAG16 (2.1%), ERBB4 (3 SNPs≈1.4% each), IKZF2 (1.4%), and PARD3B (1.0%) loci. In conditional linkage analysis, 6 SNPs from the final regression model ( CREB1, FASTKD2, MAP2, ERBB4, IKZF2 , and PARD3B ) accounted for the original linkage signal: The log of the odds score dropped from 2.10 to 0.41 after adjusting for all 6 SNPs. Functional studies revealed that the common allele of rs2253206 exhibits significantly ( P Conclusions— Our data suggest that functional DNA sequence variation in the CREB1 locus is strongly associated with ΔHR50 and explains a considerable proportion of the quantitative trait locus variance. However, at least 5 additional SNPs seem to be required to fully account for the original linkage signal.

Predicting adult body mass index-specific metabolic risk from childhood.

Abstract: Background: Metabolic risk varies within adult body mass index (BMI) categories; however, the development of BMI-specific metabolic risk from childhood is unknown. Methods: The sample included 895 adults (20–38 years of age; 43% male, 34% black) from the Bogalusa Heart Study (1995–2002), who had been measured as children (5–18 years of age) in 1981–1982. Adult metabolic risk was assessed using two definitions: Cardiometabolic risk factor clustering (RFC) included two or more abnormal risk factors [blood pressure, high-density lipoprotein cholesterol (HDL-C), triglycerides, and fasting glucose] and insulin resistance (IR), comprising the top quartile of the homeostasis model of insulin resistance (HOMA-IR) distribution. Logistic regression, within BMI categories, was used to predict adult metabolic risk from childhood mean arterial pressure (MAP), HDL-C, low-density lipoprotein cholesterol (LDL-C), glucose, and triglycerides. Covariates included childhood age, race, sex, adult BMI, and length of follow-up....

Combining genetic markers and clinical risk factors improves the risk assessment of impaired glucose metabolism.

Abstract: Background. Although several candidate gene polymorphisms (SNPs) have been associated with increased risk of type 2 diabetes mellitus (T2DM), relatively few studies have assessed the ability of T2DM candidate genes to assess the risk of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and T2DM beyond the information provided by clinical risk factors.Objective. To test whether the inclusion of genetic markers in a regression model provides a better assessment of the risk of IFG, IGT, and T2DM than a model based only on non-genetic risk factors commonly assessed in clinical settings. Methods. Subjects (n = 485; 213 parents, 272 offspring) from the Quebec Family Study, not known to haveT2DM, were measured for several risk factors and underwent an oral glucose tolerance test. Thirty-eight SNPs in 25 susceptibility/ candidate genes previously reported to be associated with T2DM were genotyped. In order to identify risk factors associated with IFG/IGT/T2DM, two logistic regression model...

Association of Single-Nucleotide Polymorphisms From 17 Candidate Genes With Baseline Symptom-Limited Exercise Test Duration and Decrease in Duration Over 20 Years The Coronary Artery Risk Development in Young Adults (CARDIA) Fitness Study

Abstract: Background— It is not known whether the genes involved with endurance performance during young adulthood are also involved with changes in performance. We examined the associations of gene variants with symptom-limited exercise test duration at baseline and decrease in duration over 20 years. Methods and Results— A total of 3783 (1835 black, 1948 white) and 2335 (1035 black, 1300 white) participants from the Coronary Artery Risk Development in Young Adults study were included in the baseline and 20-year models, respectively. Two hundred seventeen single-nucleotide polymorphisms (SNPs) in black participants and 171 in white participants from 17 genes were genotyped. In blacks, 5 SNPs in the ATP1A2 , HIF1A , NOS3 , and PPARGC1A loci tended to be associated ( P <0.05) with baseline duration in a multivariate regression model. Blacks (n=99) with at least 4 of the most-favorable genotypes at these loci had an ≈2-minute longer baseline duration than those with only 2 such genotypes ( P <0.0001). In whites, the HIF1A rs1957757 and PPARGC1A rs3774909 markers tended to be associated with baseline duration, but the association of a multimarker construct of the most-favorable genotypes at both SNPs with baseline duration was not statistically significant. In whites, 4 SNPs in the AGT , AMPD1 , ANG , and PPARGC1A loci tended to be associated with decrease in exercise duration over 20 years, and those with all 4 favorable genotypes (n=40) had a 0.8-minute less decline in duration compared with those with none or 1 (n=232) ( P <0.0001). Conclusions— In multimarker constructs, alleles at genes related to skeletal muscle Na+/K+ transport, hypoxia, and mitochondrial metabolism are associated with symptom-limited exercise test duration over time in adults.

Fine mapping of the insulin-induced gene 2 identifies a variant associated with LDL cholesterol and total apolipoprotein B levels.

Abstract: Background— In a whole-genome scan, a single nucleotide polymorphism (SNP) (rs7566605) upstream of the insulin-induced gene 2 ( INSIG2 ) was shown to influence body mass index and obesity in the Framingham Heart Study, with replication of these results in an additional 4 of 5 studies. However, other studies could not replicate the association. Because INSIG2 plays an important role in cholesterol biosynthesis, we hypothesized that human INSIG2 variants might play a role in the regulation of plasma lipid and lipoprotein levels. Methods and Results— We selected tagging SNPs spanning >100 kb of INSIG2 locus and sequenced 18 434 base pairs to discover novel SNPs. Thirty-two SNPs were genotyped in 645 individuals from the Quebec Family Study. Two SNPs (rs10490626 and rs12464355) were associated with plasma low-density lipoprotein cholesterol (LDL-C) ( P <0.0015) and total apolipoprotein B (apoB) levels ( P <0.014), whereas no association was found between any SNP and body mass index. We replicated the finding of rs10490626 for both LDL-C and total apoB in additional study samples, including 758 individuals from Saguenay–Lac St. Jean, Quebec ( P =0.040 for LDL-C, P =0.044 for apoB), 3247 Europeans ( P =0.028 for LDL-C, P =0.030 for apoB), and 1695 South Asians ( P =0.0036 for LDL-C, P =0.034 for apoB) from the INTERHEART study (for LDL-C, the combined 2-sided P =6.2×10−5 and for total apoB, P =0.0011). Furthermore, we identified a variant in the human sorbin and SH3-domain–containing-1 gene that was associated with INSIG2 mRNA levels, and this SNP was shown to act in combination with rs10490626 to affect LDL-C ( P =0.022) in the Quebec Family Study and in INTERHEART South Asians ( P =0.019) and Europeans ( P =0.052). Conclusion— These results suggest that INSIG2 genetic variants may have a more direct role in lipid and lipoprotein metabolism than in obesity.

Genes and obesity

Abstract: A number of genes have been identified that are associated with an increased body mass index (BMI), the standard measurement of obesity. By analyzing these genes, researchers hope to gain a better understanding of what causes obesity and develop ways to tackle the problem. The study of genes and obesity could lead to new treatments. This volume reviews the latest developments in the field. * This series provides a forum for discussion of new discoveries, approaches, and ideas * Contributions from leading scholars and industry experts * Reference guide for researchers involved in molecular biology and related fields

Genetics and genomics of obesity: current status.

Abstract: Publisher Summary It is commonly recognized that the prevalence of overweight and obesity is increasing around the world and that the obese are becoming more severely obese. Current estimates suggest that there are more than one billion adults who are overweight or obese worldwide. Recognizing the threat associated with excess weight, the World Health Organization has identified overweight as one of the main risk factors for the overall burden of disease in the world and one of the top five in developed nations. There are four major classes of factors contributing to the ongoing epidemic of obesity, which is ultimately the result of widespread energy imbalance favoring storage of the energy surplus not expended. These four broad classes of factors can be labeled as follows: built environment, social environment, behavior, and biology. The book Progress in Molecular Biology and Translational Science , Volume 94 reviews the latest evidence for the contribution of genetic factors to the risk of obesity. It explores genes and pathways potentially involved and the behavior that they influence and the role of genetic variation in white and brown adipose tissue biology, excess adipose tissue mass, syndromic and nonsyndromic obesity cases, lipodystrophies the current understanding of the genetic basis of eating disorders, eating behavior, and physical activity level.

Genes and obesity. Preface.

Abstract: A volume entirely devoted to the recent advances on the genetics and molecular biology of obesity is highly relevant to the serial Progress in Molecular Biology and Translational Science (PMBTS). We have been able to assemble a panel of distinguished authors for this volume, and I express my gratitude to them for a timely delivery of their contributions. The leadership of the PMBTS publication series has been a delight to work with. I express my thanks to Dr. Michael Conn, Editor of the PMBTS serial, who first came up with the suggestion of a volume devoted to obesity. I also benefited greatly from the support of Janice Hackenberg and subsequently Lisa Tickner, Acquisition Editors, Delsy Retchagar, Developmental Editor, and Vijayaraj Purush, Project Manager, all at Elsevier Inc. They were very supportive during the development of the book manuscript. Finally, I would not have been able to undertake the task of serving as editor for this volume without the outstanding and competent support of Nina Laidlaw and later Allison Templet in my office at the Pennington Biomedical Research Center. They worked diligently with each author to ensure that the manuscript was complete and met all the requirements of the publisher.