Showing papers by "Claude Bouchard published in 2012"

Bariatric Surgery and Long-term Cardiovascular Events

Abstract: Context Obesity is a risk factor for cardiovascular events. Weight loss might protect against cardiovascular events, but solid evidence is lacking. Objective To study the association between bariatric surgery, weight loss, and cardiovascular events. Design, Setting, and Participants The Swedish Obese Subjects (SOS) study is an ongoing, nonrandomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls who received usual care. Patients were recruited between September 1, 1987, and January 31, 2001. Date of analysis was December 31, 2009, with median follow-up of 14.7 years (range, 0-20 years). Inclusion criteria were age 37 to 60 years and a body mass index of at least 34 in men and at least 38 in women. Exclusion criteria were identical in surgery and control patients. Surgery patients underwent gastric bypass (13.2%), banding (18.7%), or vertical banded gastroplasty (68.1%), and controls received usual care in the Swedish primary health care system. Physical and biochemical examinations and database cross-checks were undertaken at preplanned intervals. Main Outcome Measures The primary end point of the SOS study (total mortality) was published in 2007. Myocardial infarction and stroke were predefined secondary end points, considered separately and combined. Results Bariatric surgery was associated with a reduced number of cardiovascular deaths (28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group; adjusted hazard ratio [HR], 0.47; 95% CI, 0.29-0.76; P = .002). The number of total first time (fatal or nonfatal) cardiovascular events (myocardial infarction or stroke, whichever came first) was lower in the surgery group (199 events among 2010 patients) than in the control group (234 events among 2037 patients; adjusted HR, 0.67; 95% CI, 0.54-0.83; P Conclusion Compared with usual care, bariatric surgery was associated with reduced number of cardiovascular deaths and lower incidence of cardiovascular events in obese adults.

Bariatric Surgery and Long-term Cardiovascular Events

Abstract: Context Obesity is a risk factor for cardiovascular events. Weight loss might protect against cardiovascular events, but solid evidence is lacking. Objective To study the association between bariatric surgery, weight loss, and cardiovascular events. Design, Setting, and Participants The Swedish Obese Subjects (SOS) study is an ongoing, nonrandomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls who received usual care. Patients were recruited between September 1, 1987, and January 31, 2001. Date of analysis was December 31, 2009, with median follow-up of 14.7 years (range, 0-20 years). Inclusion criteria were age 37 to 60 years and a body mass index of at least 34 in men and at least 38 in women. Exclusion criteria were identical in surgery and control patients. Surgery patients underwent gastric bypass (13.2%), banding (18.7%), or vertical banded gastroplasty (68.1%), and controls received usual care in the Swedish primary health care system. Physical and biochemical examinations and database cross-checks were undertaken at preplanned intervals. Main Outcome Measures The primary end point of the SOS study (total mortality) was published in 2007. Myocardial infarction and stroke were predefined secondary end points, considered separately and combined. Results Bariatric surgery was associated with a reduced number of cardiovascular deaths (28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group; adjusted hazard ratio [HR], 0.47; 95% CI, 0.29-0.76; P = .002). The number of total first time (fatal or nonfatal) cardiovascular events (myocardial infarction or stroke, whichever came first) was lower in the surgery group (199 events among 2010 patients) than in the control group (234 events among 2037 patients; adjusted HR, 0.67; 95% CI, 0.54-0.83; P Conclusion Compared with usual care, bariatric surgery was associated with reduced number of cardiovascular deaths and lower incidence of cardiovascular events in obese adults.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Abstract: Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Bariatric Surgery and Prevention of Type 2 Diabetes in Swedish Obese Subjects

Abstract: BACKGROUND Weight loss protects against type 2 diabetes but is hard to maintain with behavioral modification alone. In an analysis of data from a nonrandomized, prospective, controlled study, we examined the effects of bariatric surgery on the prevention of type 2 diabetes. METHODS In this analysis, we included 1658 patients who underwent bariatric surgery and 1771 obese matched controls (with matching performed on a group, rather than individual, level). None of the participants had diabetes at baseline. Patients in the bariatric-surgery cohort underwent banding (19%), vertical banded gastroplasty (69%), or gastric bypass (12%); nonrandomized, matched, prospective controls received usual care. Participants were 37 to 60 years of age, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was 34 or more in men and 38 or more in women. This analysis focused on the rate of incident type 2 diabetes, which was a prespecified secondary end point in the main study. At the time of this analysis (January 1, 2012), participants had been followed for up to 15 years. Despite matching, some baseline characteristics differed significantly between the groups; the baseline body weight was higher and risk factors were more pronounced in the bariatric-surgery group than in the control group. At 15 years, 36.2% of the original participants had dropped out of the study, and 30.9% had not yet reached the time for their 15-year follow-up examination. RESULTS During the follow-up period, type 2 diabetes developed in 392 participants in the control group and in 110 in the bariatric-surgery group, corresponding to incidence rates of 28.4 cases per 1000 person-years and 6.8 cases per 1000 person-years, respectively (adjusted hazard ratio with bariatric surgery, 0.17; 95% confidence interval, 0.13 to 0.21; P<0.001). The effect of bariatric surgery was influenced by the presence or absence of impaired fasting glucose (P = 0.002 for the interaction) but not by BMI (P = 0.54). Sensitivity analyses, including end-point imputations, did not change the overall conclusions. The postoperative mortality was 0.2%, and 2.8% of patients who underwent bariatric surgery required reoperation within 90 days owing to complications. CONCLUSIONS Bariatric surgery appears to be markedly more efficient than usual care in the prevention of type 2 diabetes in obese persons. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01479452.)

Bariatric Surgery and Prevention of Type 2 Diabetes in Swedish Obese Subjects

Abstract: BACKGROUND Weight loss protects against type 2 diabetes but is hard to maintain with behavioral modification alone. In an analysis of data from a nonrandomized, prospective, controlled study, we examined the effects of bariatric surgery on the prevention of type 2 diabetes. METHODS In this analysis, we included 1658 patients who underwent bariatric surgery and 1771 obese matched controls (with matching performed on a group, rather than individual, level). None of the participants had diabetes at baseline. Patients in the bariatric-surgery cohort underwent banding (19%), vertical banded gastroplasty (69%), or gastric bypass (12%); nonrandomized, matched, prospective controls received usual care. Participants were 37 to 60 years of age, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was 34 or more in men and 38 or more in women. This analysis focused on the rate of incident type 2 diabetes, which was a prespecified secondary end point in the main study. At the time of this analysis (January 1, 2012), participants had been followed for up to 15 years. Despite matching, some baseline characteristics differed significantly between the groups; the baseline body weight was higher and risk factors were more pronounced in the bariatric-surgery group than in the control group. At 15 years, 36.2% of the original participants had dropped out of the study, and 30.9% had not yet reached the time for their 15-year follow-up examination. RESULTS During the follow-up period, type 2 diabetes developed in 392 participants in the control group and in 110 in the bariatric-surgery group, corresponding to incidence rates of 28.4 cases per 1000 person-years and 6.8 cases per 1000 person-years, respectively (adjusted hazard ratio with bariatric surgery, 0.17; 95% confidence interval, 0.13 to 0.21; P<0.001). The effect of bariatric surgery was influenced by the presence or absence of impaired fasting glucose (P = 0.002 for the interaction) but not by BMI (P = 0.54). Sensitivity analyses, including end-point imputations, did not change the overall conclusions. The postoperative mortality was 0.2%, and 2.8% of patients who underwent bariatric surgery required reoperation within 90 days owing to complications. CONCLUSIONS Bariatric surgery appears to be markedly more efficient than usual care in the prevention of type 2 diabetes in obese persons. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01479452.)

Adverse metabolic response to regular exercise: Is it a rare or common occurrence?

Abstract: Background: Individuals differ in the response to regular exercise. Whether there are people who experience adverse changes in cardiovascular and diabetes risk factors has never been addressed. Methodology/Principal Findings: An adverse response is defined as an exercise-induced change that worsens a risk factor beyond measurement error and expected day-to-day variation. Sixty subjects were measured three times over a period of three weeks, and variation in resting systolic blood pressure (SBP) and in fasting plasma HDL-cholesterol (HDL-C), triglycerides (TG), and insulin (FI) was quantified. The technical error (TE) defined as the within-subject standard deviation derived from these measurements was computed. An adverse response for a given risk factor was defined as a change that was at least two TEs away from no change but in an adverse direction. Thus an adverse response was recorded if an increase reached 10 mm Hg or more for SBP, 0.42 mmol/L or more for TG, or 24 pmol/L or more for FI or if a decrease reached 0.12 mmol/L or more for HDL-C. Completers from six exercise studies were used in the present analysis: Whites (N = 473) and Blacks (N = 250) from the HERITAGE Family Study; Whites and Blacks from DREW (N = 326), from INFLAME (N = 70), and from STRRIDE (N = 303); and Whites from a University of Maryland cohort (N = 160) and from a University of Jyvaskyla study (N = 105), for a total of 1,687 men and women. Using the above definitions, 126 subjects (8.4%) had an adverse change in FI. Numbers of adverse responders reached 12.2% for SBP, 10.4% for TG, and 13.3% for HDL-C. About 7% of participants experienced adverse responses in two or more risk factors. Conclusions/Significance: Adverse responses to regular exercise in cardiovascular and diabetes risk factors occur. Identifying the predictors of such unwarranted responses and how to prevent them will provide the foundation for personalized exercise prescription.

Why do individuals not lose more weight from an exercise intervention at a defined dose? An energy balance analysis

Abstract: Weight loss resulting from an exercise intervention tends to be lower than predicted. Modest weight loss can arise from an increase in energy intake, physiological reductions in resting energy expenditure, an increase in lean tissue or a decrease in non-exercise activity. Lower than expected, weight loss could also arise from weak and invalidated assumptions within predictive models. To investigate these causes, we systematically reviewed studies that monitored compliance to exercise prescriptions and measured exercise-induced change in body composition. Changed body energy stores were calculated to determine the deficit between total daily energy intake and energy expenditures. This information combined with available measurements was used to critically evaluate explanations for low exercise-induced weight loss. We conclude that the small magnitude of weight loss observed from the majority of evaluated exercise interventions is primarily due to low doses of prescribed exercise energy expenditures compounded by a concomitant increase in caloric intake.

Genomic predictors of trainability.

Abstract: The concept of individual differences in the response to exercise training or trainability was defined three decades ago. In a series of experimental studies with pairs of monozygotic twins, evidence was found in support of a strong genotype dependency of the ability to respond to regular exercise. In the HERITAGE Family Study, it was observed that the heritability of the maximal oxygen uptake response to 20 weeks of standardized exercise training reached 47% after adjustment for age, sex, baseline maximal oxygen uptake and baseline body mass and composition. Candidate gene studies have not yielded as many validated gene targets and variants as originally anticipated. Genome-wide explorations have generated more convincing predictors of maximal oxygen uptake trainability. A genomic predictor score based on the number of favourable alleles carried at 21 single nucleotide polymorphisms appears to be able to identify low and high training response classes that differ by at least threefold. Combining transcriptomic and genomic technologies has also yielded highly promising results concerning the ability to predict trainability among sedentary people.

Anthropometric Correlates of Total Body Fat, Abdominal Adiposity, and Cardiovascular Disease Risk Factors in a Biracial Sample of Men and Women

Abstract: Objective To investigate associations between anthropometric measurements and total body fat, abdominal adipose tissue, and cardiovascular disease risk factors in a large biracial sample.

Bariatric Surgery and Long-Term Cardiovascular Events

Abstract: Context Obesity is a risk factor for cardiovascular events. Weight loss might protect against cardiovascular events, but solid evidence is lacking. Objective To study the association between bariatric surgery, weight loss, and cardiovascular events. Design, Setting, and Participants The Swedish Obese Subjects (SOS) study is an ongoing, nonrandomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls who received usual care. Patients were recruited between September 1, 1987, and January 31, 2001. Date of analysis was December 31, 2009, with median follow-up of 14.7 years (range, 0-20 years). Inclusion criteria were age 37 to 60 years and a body mass index of at least 34 in men and at least 38 in women. Exclusion criteria were identical in surgery and control patients. Surgery patients underwent gastric bypass (13.2%), banding (18.7%), or vertical banded gastroplasty (68.1%), and controls received usual care in the Swedish primary health care system. Physical and biochemical examinations and database cross-checks were undertaken at preplanned intervals. Main Outcome Measures The primary end point of the SOS study (total mortality) was published in 2007. Myocardial infarction and stroke were predefined secondary end points, considered separately and combined. Results Bariatric surgery was associated with a reduced number of cardiovascular deaths (28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group; adjusted hazard ratio [HR], 0.47; 95% CI, 0.29-0.76; P = .002). The number of total first time (fatal or nonfatal) cardiovascular events (myocardial infarction or stroke, whichever came first) was lower in the surgery group (199 events among 2010 patients) than in the control group (234 events among 2037 patients; adjusted HR, 0.67; 95% CI, 0.54-0.83; P Conclusion Compared with usual care, bariatric surgery was associated with reduced number of cardiovascular deaths and lower incidence of cardiovascular events in obese adults.

Longer sleep duration associates with lower adiposity gain in adult short sleepers

Abstract: The objective of this longitudinal, observational study was to verify whether a favorable change in sleep duration over 6 years could impact objective indicators of adiposity in adults aged 18–64 years. Short-duration sleepers (⩽6 h per day; n=43) at baseline were divided into two groups: (i) those who increased their sleep duration to a ‘healthy’ length of 7–8 h per day at year 6 (mean increase: 1.52±0.66 h per day; n=23); and (ii) those who maintained their short sleep duration habits (mean change: −0.11±0.38 h per day; n=20). Adult individuals who reported sleeping 7–8 h per day at both baseline and year 6 (n=173) were used as a control group. Change in adiposity indicators for each sleep-duration group was compared by analysis of covariance. We observed that the two short-sleep-duration groups had similar baseline characteristics. However, short-duration sleepers who maintained their short sleep duration experienced a greater increase in body mass index (BMI) (difference: 1.1±0.36 kg m−2, P<0.05) and fat mass (difference: 2.4±0.64 kg, P<0.05) over the 6-year follow-up period than short-duration sleepers who increased their sleep duration, even after adjustment for relevant covariates. We did not observe any significant difference in adiposity changes between the control group and short-duration sleepers who increased their sleep duration. This study suggests for the first time that shifting sleep duration from a short to a healthier length is associated with an attenuation of fat mass gain.

Advances in exercise, fitness, and performance genomics in 2011.

Abstract: This review of the exercise genomics literature emphasizes the highest quality articles published in 2011. Given this emphasis on the best publications, only a small number of published articles are reviewed. One study found that physical activity levels were significantly lower in patients with mitochondrial DNA mutations compared with controls. A two-stage fine-mapping follow-up of a previous linkage peak found strong associations between sequence variation in the activin A receptor, type-1B (ACVRIB) gene and knee extensor strength, with rs2854464 emerging as the most promising candidate polymorphism. The association of higher muscular strength with the rs2854464 A allele was confirmed in two separate cohorts. A study using a combination of transcriptomic and genomic data identified a comprehensive map of the transcriptomic features important for aerobic exercise training-induced improvements in maximal oxygen consumption, but no genetic variants derived from candidate transcripts were associated with trainability. A large-scale de novo meta-analysis confirmed that the effect of sequence variation in the fat mass and obesity-associated (FTO) gene on the risk of obesity differs between sedentary and physically active adults. Evidence for gene-physical activity interactions on type 2 diabetes risk was found in two separate studies. A large study of women found that physical activity modified the effect of polymorphisms in the lipoprotein lipase (LPL), hepatic lipase (LIPC), and cholesteryl ester transfer protein (CETP) genes, identified in previous genome-wide association study reports, on HDL cholesterol. We conclude that a strong exercise genomics corpus of evidence would not only translate into powerful genomic predictors but also have a major effect on exercise biology and exercise behavior research.

Abdominal obesity and mortality: The Pennington Center Longitudinal Study.

Abstract: The purpose of this study was to determine the association between visceral adipose tissue (VAT) and all-cause mortality. The sample included 1089 white men and women 18–84 years of age from the Pennington Center Longitudinal Study, a prospective cohort of participants assessed between 1995 and 2008, and followed for mortality until 31 December 2009. Abdominal VAT was measured at the L4–L5 vertebral level using computed tomography. There were 27 deaths during an average of 9.1 years of follow-up. Abdominal VAT was significantly associated with mortality after adjustment for age, sex and year of examination (hazards ratio (HR) 1.46; 95% confidence interval 1.05–2.05). The association was stronger after the inclusion of abdominal subcutaneous adipose tissue (SAT), smoking status, alcohol consumption and leisure-time physical activity as additional covariates (HR 1.74; 1.17–2.59). Limiting the sample to participants who were free of stroke, heart disease and cancer at baseline reduced the strength of the relationship slightly (HR 1.62; 1.07–2.47). Abdominal SAT was not associated with mortality, either alone or in combination with VAT and other covariates. The results support the assertion that abdominal VAT is an important therapeutic target for obesity reduction efforts.

Heritability of submaximal exercise heart rate response to exercise training is accounted for by nine SNPs.

Abstract: Endurance training-induced changes in hemodynamic traits are heritable. However, few genes associated with heart rate training responses have been identified. The purpose of our study was to perform a genome-wide association study to uncover DNA sequence variants associated with submaximal exercise heart rate training responses in the HERITAGE Family Study. Heart rate was measured during steady-state exercise at 50 W (HR50) on 2 separate days before and after a 20-wk endurance training program in 483 white subjects from 99 families. Illumina HumanCNV370-Quad v3.0 BeadChips were genotyped using the Illumina BeadStation 500GX platform. After quality control procedures, 320,000 single-nucleotide polymorphisms (SNPs) were available for the genome-wide association study analyses, which were performed using the MERLIN software package (single-SNP analyses and conditional heritability tests) and standard regression models (multivariate analyses). The strongest associations for HR50 training response adjusted for age, sex, body mass index, and baseline HR50 were detected with SNPs at the YWHAQ locus on chromosome 2p25 (P = 8.1 × 10(-7)), the RBPMS locus on chromosome 8p12 (P = 3.8 × 10(-6)), and the CREB1 locus on chromosome 2q34 (P = 1.6 × 10(-5)). In addition, 37 other SNPs showed P values <9.9 × 10(-5). After removal of redundant SNPs, the 10 most significant SNPs explained 35.9% of the ΔHR50 variance in a multivariate regression model. Conditional heritability tests showed that nine of these SNPs (all intragenic) accounted for 100% of the ΔHR50 heritability. Our results indicate that SNPs in nine genes related to cardiomyocyte and neuronal functions, as well as cardiac memory formation, fully account for the heritability of the submaximal heart rate training response.

Fundamentals of nutrigenetics and nutrigenomics.

Abstract: This volume of Progress in Molecular Biology and Translational Science is devoted to the exciting and promising field of nutrigenetics and nutrigenomics. The introductory chapter defines the basic concepts necessary for the interpretation of the material covered in the remainder of the volume. Emphasis is on the concept of personalized nutrition and its likely role in public health and disease prevention, as well as in therapeutics. Nutrigenetics refers to the role of DNA sequence variation in the responses to nutrients, whereas nutrigenomics is the study of the role of nutrients in gene expression. This research is predicated on the assumption that there are individual differences in responsiveness to acute or repeated exposures to a given nutrient or combination of nutrients. Throughout human history, diet has affected the expression of genes, resulting in phenotypes that are able to successfully respond to environmental challenges and that allow better exploitation of food resources. These adaptations have been key to human growth and development. Technological advances have made it possible to investigate not only specific genes but also to explore in unbiased designs the whole genome-wide complement of DNA sequence variants or transcriptome. These advances provide an opportunity to establish the foundation for incorporating biological individuality into dietary recommendations, with significant therapeutic potential.

Performance of genotype imputations using data from the 1000 Genomes Project.

Abstract: Genotype imputations based on 1000 Genomes (1KG) Project data have the advantage of imputing many more SNPs than imputations based on HapMap data. It also provides an opportunity to discover associations with relatively rare variants. Recent investigations are increasingly using 1KG data for genotype imputations, but only limited evaluations of the performance of this approach are available. In this paper, we empirically evaluated imputation performance using 1KG data by comparing imputation results to those using the HapMap Phase II data that have been widely used. We used three reference panels: the CEU panel consisting of 120 haplotypes from HapMap II and 1KG data (June 2010 release) and the EUR panel consisting of 566 haplotypes also from 1KG data (August 2010 release). We used Illumina 324,607 autosomal SNPs genotyped in 501 individuals of European ancestry. Our most important finding was that both 1KG reference panels provided much higher imputation yield than the HapMap II panel. There were more than twice as many successfully imputed SNPs as there were using the HapMap II panel (6.7 million vs. 2.5 million). Our second most important finding was that accuracy using both 1KG panels was high and almost identical to accuracy using the HapMap II panel. Furthermore, after removing SNPs with MACH Rsq <0.3, accuracy for both rare and low frequency SNPs was very high and almost identical to accuracy for common SNPs. We found that imputation using the 1KG-EUR panel had advantages in successfully imputing rare, low frequency and common variants. Our findings suggest that 1KG-based imputation can increase the opportunity to discover significant associations for SNPs across the allele frequency spectrum. Because the 1KG Project is still underway, we expect that later versions will provide even better imputation performance.

A variant in the LRRFIP1 gene is associated with adiposity and inflammation

Abstract: Inflammation is an important factor linking abdominal obesity with insulin resistance and related cardiometabolic risk. A genome-wide association study of adiposity-related traits performed in the Quebec Family Study (QFS) revealed that a single-nucleotide polymorphism (SNP) in the LRRFIP1 gene (rs11680012) was associated with abdominal adiposity (P = 4.6 × 10–6). Objective: The objective of this study was to assess the relationship between polymorphisms in LRRFIP1 gene and adiposity (BMI, fat mass (FM), waist circumference (WC), and computed tomography-derived areas of total, subcutaneous and visceral abdominal adipose tissue) and markers of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)). Design and Methods: Using Sequenom, 16 tag SNPs in the LRRFIP1 gene, capturing 78% of the genetic variation, were genotyped in 926 participants of the QFS. Results: Eight SNPs (rs7575941, rs3769053, rs11689421, rs3820808, rs11680012, rs3806505, rs6739130, and rs11686141) showed evidence of association with at least two adiposity phenotypes and plasma levels of one marker of inflammation. The strongest evidence of association was observed with rs11680012, which explained 1.8–3.4% of the variance in areas of abdominal adiposity and 2.0% of the variation in CRP levels. Carriers of the rare allele of rs11680012 had ∼30% more abdominal adiposity (P values between 2.7 × 10–4 and 3.8 × 10–6) and 75% higher CRP levels (P = 1.6 × 10–4) than the common allele in age and sex adjusted data. Rs11680012 is a G/C SNP converting an arginine into a threonine and this amino acid substitution may potentially alter exonic splicing. Conclusion: This gene may therefore represent a potential interesting target to investigate in further functional studies on adiposity and inflammation.

Fine mapping of a QTL on chromosome 13 for submaximal exercise capacity training response: the HERITAGE Family Study

Abstract: Although regular exercise improves submaximal aerobic capacity, there is large variability in its response to exercise training. While this variation is thought to be partly due to genetic differences, relatively little is known about the causal genes. Submaximal aerobic capacity traits in the current report include the responses of oxygen consumption (ΔVO260), power output (ΔWORK60), and cardiac output (ΔQ60) at 60% of VO2max to a standardized 20-week endurance exercise training program. Genome-wide linkage analysis in 475 HERITAGE Family Study Caucasians identified a locus on chromosome 13q for ΔVO260 (LOD = 3.11). Follow-up fine mapping involved a dense marker panel of over 1,800 single-nucleotide polymorphisms (SNPs) in a 7.9-Mb region (21.1–29.1 Mb from p-terminus). Single-SNP analyses found 14 SNPs moderately associated with both ΔVO260 at P ≤ 0.005 and the correlated traits of ΔWORK60 and ΔQ60 at P < 0.05. Haplotype analyses provided several strong signals (P < 1.0 × 10−5) for ΔVO260. Overall, association analyses narrowed the target region and included potential biological candidate genes (MIPEP and SGCG). Consistent with maximal heritability estimates of 23%, up to 20% of the phenotypic variance in ΔVO260 was accounted for by these SNPs. These results implicate candidate genes on chromosome 13q12 for the ability to improve submaximal exercise capacity in response to regular exercise. Submaximal exercise at 60% of maximal capacity is an exercise intensity that falls well within the range recommended in the Physical Activity Guidelines for Americans and thus has potential public health relevance.

Gene-exercise interactions.

Abstract: A growing body of evidence indicates that genotype-by-physical activity interactions on various health-related outcomes do exist. Observational studies have shown that relationships between DNA sequence variants and risk factors are significantly different between sedentary and physically active individuals, while exercise intervention studies have demonstrated that genetic variation contributes significantly to interindividual variation in responsiveness to exercise training. The knowledge base on gene-activity interactions will grow considerably within a few years when large observational genome-wide association study (GWAS) consortia will report their findings. Progress with exercise intervention studies will be slower because of resource requirements. However, such studies are desperately needed to fully understand the genetics as well as the exercise biology of complex traits and to confirm the gene-exercise interactions derived from observational studies. Furthermore, development of personalized exercise medicine applications will be difficult or even impossible without a proper understanding of gene-exercise interactions.

SHORT COMMUNICATION Longer sleep duration associates with lower adiposity gain in adult short sleepers

Abstract: The objective of this longitudinal, observational study was to verify whether a favorable change in sleep duration over 6 years could impact objective indicators of adiposity in adults aged 18–64 years. Short-duration sleepers (p6h per day; n ¼43) at baseline were divided into two groups: (i) those who increased their sleep duration to a ‘healthy’ length of 7–8h per day at year 6 (mean increase: 1.52±0.66h per day; n ¼23); and (ii) those who maintained their short sleep duration habits (mean change: � 0.11±0.38h per day; n ¼20). Adult individuals who reported sleeping 7–8h per day at both baseline and year 6 (n ¼173) were used as a control group. Change in adiposity indicators for each sleep-duration group was compared by analysis of covariance. We observed that the two short-sleep-duration groups had similar baseline characteristics. However, short-duration sleepers who maintained their short sleep duration experienced a greater increase in body mass index (BMI) (difference: 1.1±0.36kgm � 2 , Po0.05) and fat mass (difference: 2.4±0.64kg, Po0.05) over the 6-year follow-up period than shortduration sleepers who increased their sleep duration, even after adjustment for relevant covariates. We did not observe any significant difference in adiposity changes between the control group and short-duration sleepers who increased their sleep duration. This study suggests for the first time that shifting sleep duration from a short to a healthier length is associated with an attenuation of fat mass gain.

Past dieting is related to rigid control and disinhibition in adolescents from the Québec Family Study.

Abstract: Eating behaviour traits of rigid control and disinhibition have been associated with body weight in both adults and adolescents. Moreover, adults reporting a dieting history have increased levels of unhealthy eating behaviours. Against this background, the present study aimed to examine the relationship between dieting history and eating behaviour traits in adolescents. For the purpose of this research, a total of sixty adolescents (aged 15 (sem 2·4) years) from the Quebec Family Study completed the Three-Factor Eating Questionnaire (TFEQ) and a questionnaire regarding eating habits. Self-reported current and past dieting were analysed against eating behaviour traits measured by the TFEQ, including all subscales. As the results revealed, few adolescents reported currently dieting (n 3). Adolescents who reported a dieting history (23·3 %) were older (16·9 v. 14·4 years, P < 0·001), were more likely to be female (78·6 v. 41·3 %, P < 0·05) but did not have a significantly higher BMI z-score (1·5 v. 0·9, P = 0·10), although they were more likely to be either overweight or obese (P < 0·01). After correcting for sex, BMI and age, adolescents who reported a dieting history had higher levels of rigid control and disinhibition (P < 0·05–0·0001) than those reporting no dieting history. A greater proportion of adolescents characterised by high rigid control and high disinhibition were past dieters, compared to those characterised by low levels of both behaviour traits (53 v. 4 %). The study arrived at the following conclusions: as observed in adults, adolescents with a history of dieting present unfavourable eating behaviour traits. These behavioural traits may represent an additional challenge to the long-term regulation of body weight.

Changes in uric acid levels following bariatric surgery are not associated with SLC2A9 variants in the Swedish Obese Subjects Study.

Abstract: Context and objective Obesity and SLC2A9 genotype are strong determinants of uric acid levels. However, data on SLC2A9 variants and weight loss induced changes in uric acid levels are missing. We examined whether the changes in uric acid levels two- and ten-years after weight loss induced by bariatric surgery were associated with SLC2A9 single nucleotide polymorphisms (SNPs) in the Swedish Obese Subjects study. Methods SNPs (N = 14) identified by genome-wide association studies and exonic SNPs in the SLC2A9 gene locus were genotyped. Cross-sectional associations were tested before (N = 1806), two (N = 1664) and ten years (N = 1201) after bariatric surgery. Changes in uric acid were compared between baseline and Year 2 (N = 1660) and years 2 and 10 (N = 1172). A multiple testing corrected threshold of P = 0.007 was used for statistical significance. Results Overall, 11 of the 14 tested SLC2A9 SNPs were significantly associated with cross-sectional uric acid levels at all three time points, with rs13113918 showing the strongest association at each time point (R(2) = 3.7-5.2%, 3.9×10(-22)≤p≤7.7×10(-11)). One SNP (rs737267) showed a significant association (R(2) = 0.60%, P = 0.002) with change in uric acid levels from baseline to Year 2, as common allele homozygotes (C/C, N = 957) showed a larger decrease in uric acid (-61.4 µmol/L) compared to minor allele carriers (A/X: -51.7 µmol/L, N = 702). No SNPs were associated with changes in uric acid from years 2 to 10. Conclusions SNPs in the SLC2A9 locus contribute significantly to uric acid levels in obese individuals, and the associations persist even after considerable weight loss due to bariatric surgery. However, we found little evidence for an interaction between genotype and weight change on the response of uric acid to bariatric surgery over ten years. Thus, the fluctuations in uric acid levels among the surgery group appear to be driven by the weight losses and gains, independent of SLC2A9 genotypes.

Preface. Advances in nutrigenetics and nutrigenomics.

Abstract: This volume of Progress in Molecular Biology and Translational Science covers the recent advances in the expanding fields of nutrigenetics and nutrigenomics. Forty authors from eight countries have contributed to the publication, representing the most cutting-edge research available. * Contributions from leading authorities* Informs and updates on all the latest developments in the field