Contribution of the functional 5-HTTLPR variant of the SLC6A4 gene to obesity risk in male adults

Background: A polymorphism in the promoter region of the serotonin transporter (5‐HTTLPR) gene SLC6A4 shows functionally important 44‐bp insertion/deletion alleles: long (L) and short (S). We have previously found that the S allele is a genetic risk factor for obesity in adolescents. Objective: The aim of this study was to evaluate whether the S/L variant of the SLC6A4 gene is associated with BMI as a continuous trait and also with obesity in a large sample of adult men of European ancestry included in a cross‐sectional, population‐based study. Methods and Procedures: The study group was composed of individuals who were randomly recruited from a factory in the Buenos Aires metropolitan area and who underwent an annual health examination. Results: We observed that among 1,329 unrelated subjects, aged 34.6 ± 0.3 years, age‐adjusted BMI values (expressed as mean ± s.e.) for each genotype showed statistically significant differences across genotypic groups (LL: 25.4 ± 0.2, LS: 26.0 ± 0.1 and SS: 26.7 ± 0.2, P < 0.0002). In addition, association tests showed that the 5‐HTTLPR‐genotype distribution was significantly different between 692 lean (BMI ≤ 25 kg/m2) and 637 obese (BMI ≥ 27 kg/m2) individuals. We found a 1.36 odds ratio (OR) (95% CI 1.01–1.85) for obesity in SS carriers in comparison with LL carriers, P = 0.026. Discussion: In conclusion, our findings indicate that 5‐HTTLPR polymorphism may be linked with BMI and also with obesity and/or overweight in adult male population, reinforcing the role of the serotonin transporter as a risk factor for the obesity phenotype and suggesting potential new avenues for its pharmacological treatment.     

Weight Status Continuity and Change From Adolescence to Young Adulthood: Examining Disease and Health Risk Conditions

This study examined weight status during adolescence and young adulthood, and young adult health condition diagnosis. Data are from 10,439 African‐American, Hispanic, and white men and women participating in the National Longitudinal Study of Adolescent Health during Waves 1 (adolescence: ages 12–19) and 3 (young adulthood: ages 19–26). Categories were created differentiating individuals based on their weight status during adolescence and young adulthood: (i) obese during adolescence and young adulthood (i.e., continuously obese), (ii) obese during adolescence only, (iii) obese during young adulthood only, and (iv) never obese. Multilevel random intercept regression models were used to examine the impact of obesity category, sex, and race/ethnicity on young adult asthma, diabetes, high cholesterol, and high blood pressure. Continuous obesity increased the likelihood for young adult disease and health risk conditions compared to individuals who were never obese. Obesity isolated to adolescence (Wave 1) increased the likelihood for high cholesterol and high blood pressure, whereas obesity isolated to young adulthood (Wave 3) also increased the likelihood for diabetes—all increases were relative to nonobese weight status during both periods. Associations varied in direction and degree when sex and race/ethnicity were considered. Findings clarify some of the mixed understandings regarding the associations between age of onset and stability of obesity, and health outcomes with important public health implications. Although results indicate obesity isolated to a single developmental period does have health repercussions, obesity experienced continuously during adolescence and young adulthood greatly intensified risk across all health conditions.     

MAOA-L carriers are better at making optimal financial decisions under risk

Genes can affect behaviour towards risks through at least two distinct neurocomputational mechanisms: they may affect the value assigned to different risky options, or they may affect the way in which the brain adjudicates between options based on their value. We combined methods from neuroeconomics and behavioural genetics to investigate the impact that the genes encoding for monoamine oxidase-A (MAOA), the serotonin transporter (5-HTT) and the dopamine D4 receptor (DRD4) have on these two computations. Consistent with previous literature, we found that carriers of the MAOA-L polymorphism were more likely to take financial risks. Our computational choice model, rooted in established decision theory, showed that MAOA-L carriers exhibited such behaviour because they are able to make better financial decisions under risk, and not because they are more impulsive. In contrast, we found no behavioural or computational differences among the 5-HTT and DRD4 polymorphisms.     

Epigenetic Regulation of Serotonin Transporter in Psychiatric Disorders

SLC6A4 (solute carrier family 6,member 4) gene encodes a serotonin transporter (5-hydroxytryptamine transporter,HTT),which transports synaptic serotonin into presynaptic terminal.SLC6A4 is known to be the target of antidepressants such as selective serotonin reuptake inhibitors (SSRIs).Inhibition of HTT increases synaptic serotonin concentration and thereby exerts antidepressant efficacy.A large number of genetic studies suggest the contribution of genetic variations of SLC6A4 to various psychiatric disorders.The most studied genetic variation,HTT-linked polymorphic region (HTTLPR),is located at the promoter region of SLC6A4.     

The Changing Body Mass–Mortality Association in the United States: Evidence of Sex-Specific Cohort Trends from Three National Health and Nutrition Examination Surveys

The association between body mass index (BMI) categories and mortality remains uncertain. Using three National Health and Nutrition Examination Surveys covering the 1971–2006 period for cohorts born between 1896 and 1968, this study estimates separately for men and women models for year-of-birth (cohort) and year-of-observation (period) trends in how age-specific mortality rates differ across BMI categories. Among women, relative to the normal weight (BMI 18.5–24.9 kg/m²), there are increasing trends in mortality rates for the overweight (BMI 25–29.9) or obese (BMI ≥ 30). Among men, mortality rates relative to the normal weight decrease for the overweight, do not change for the moderately obese (BMI 30–34.9), and increase for the severely obese (BMI ≥ 35). Period and cohort trends are similar, but the cohort trends are more consistent. In the latest cohorts, compared with the normal weight, mortality rates are 50 percent lower for overweight men, not different for moderately obese men, and 100–200 percent higher for severely obese men and for overweight or obese women. For U.S. cohorts born after the 1920s, a lower overweight than normal weight mortality is confined to men. I speculate on possible reasons why the mortality association with overweight and obesity varies by sex and cohort.     

Body mass index gain, fast food, and physical activity: effects of shared environments over time

Objective : The magnitude of environmental vs. genetic effects on BMI, diet, and physical activity (PA) is widely debated. We followed a sibling cohort (where individuals shared households in childhood and adolescence) to young adulthood (when some continued sharing households and others lived apart) to examine the role of discordant environments in adult twins’ divergent trends in BMI and health behaviors and to quantify the variation in BMI and behavior among all siblings that is attributable to environmental and additive genetic effects. Research Methods and Procedures : In the National Longitudinal Study of Adolescent Health, siblings sharing households for ≥10 years as adolescents (mean age = 16.5 ± 1.7 years; N = 5524) were followed into adulthood (mean = 22.4 ± 1.8 years; N = 4368), self‐reporting PA, sedentary behavior, and dietary characteristics. Adult BMI and adolescent z scores were derived from measured height and weight. Results : Compared with those living together, twins living apart exhibited greater discordance in change in BMI, PA, and fast food intake from adolescence to adulthood. Adolescent household environments accounted for 8% to 10% of variation in adolescent fast food intake and sedentary behaviors and 50% of variation in adolescent overweight. Adolescent household effects on PA were substantially greater in young adulthood (accounting for 50% of variation) vs. adolescence. Young adult fast food intake was significantly affected by young adult household environment, accounting for 12% of variation. Discussion : These findings highlight important environmental influences on BMI, PA, and fast food intake during the transition to adulthood. Household and physical environments play an important role in establishing long‐term behavior patterns.     

Adolescents' perceived weight associated with depression in young adulthood: a longitudinal study

Objective: The objective of this study is to examine whether adolescents’ measured BMI and self‐ or mother's perception of weight status at age 14 are associated with depression at age 21. Research Methods and Procedures: The study participants were a subsample of 2017 participants of the Mater–University of Queensland Study of Pregnancy and Its Outcomes, a population‐based birth cohort study, which commenced in 1981 in Brisbane, Australia, for whom measured BMI at ages 14 and 21 and information on self‐reported mental health problems were available at the age 21 follow‐up. A total of 1802 individuals had measured BMI and reported weight perception in a supplementary questionnaire at 14 years, and their self‐reported mental health problems were reported at 21 years. Mental health was measured using Center for Epidemiology Studies Depression Scale and Young Adults Self‐Reported depression/anxiety at 21 years of age. Results: We found that both young adult males and females who perceived themselves as overweight at age 14 had more mental health problems compared with those who perceived themselves as the right weight. When we combined adolescents’ weight perception with their measured BMI categories, weight perception but not measured overweight was associated with mental health problems for males and females at age 21. This association remained after adjusting for potential confounders, including adolescents’ behavioral problems, family meals, diet, physical activity, and television watching. Conclusions: This study suggests that the perception of being overweight during adolescence is a significant risk factor for depression in young adult men and women. The perception of being overweight during adolescence should be considered a possible target for a prevention intervention.     

Weight Status in Childhood as a Predictor of Becoming Overweight or Hypertensive in Early Adulthood**

Objective: To assess the extent to which weight status in childhood or adolescence predicts becoming overweight or hypertensive by young adulthood. Research Methods and Procedures: We conducted a prospective study of 314 children, who were 8 to 15 years old at baseline, and were followed up 8 to 12 years later. Weight, height, and blood pressure were measured by trained research staff. Incident overweight was defined as BMI ≥ 25 kg/m² among participants who had not been overweight as children. Results: More male subjects (48.3%) than female subjects (23.5%) became overweight or obese between their first childhood visit and the young adult follow‐up (p < 0.001). Being in the upper one half of the normal weight range (i.e., BMI between the 50th and 84th percentiles for age and gender in childhood) was a good predictor of becoming overweight as a young adult. Compared with children with a BMI <50th percentile, girls and boys between the 50th and 74th percentiles of BMI were ～5 times more likely [boys, odds ratio (OR) = 5.3, p = 0.002; girls, OR = 4.8, p = 0.07] and those with a BMI between the 75th and 84th percentiles were up to 20 times more likely (boys, OR = 4.3, p = 0.02; girls, OR = 20.2, p = 0.001) to become overweight. The incidence of high blood pressure was greater among the male subjects (12.3% vs. 1.9%). Compared with boys who had childhood BMI below the 75th percentile, boys between the 75th and 85th percentiles of BMI as children were four times more likely (OR = 3.6) and those at above the 85th percentile were five times more likely (OR = 5.1) to become hypertensive. Discussion: High normal weight status in childhood predicted becoming overweight or obese as an adult. Also, among the boys, elevated BMI in childhood predicted risk of hypertension in young adulthood.     

Investigation of 17 candidate genes for personality traits confirms effects of the HTR2A gene on novelty seeking

Genes involved in serotonergic and dopaminergic neurotransmission have been hypothesized to affect different aspects of personality, but findings from genetic association studies did not provide conclusive results so far. In previous studies, however, only one or a few polymorphisms within single genes were investigated neglecting the possibility that the genetic associations might be more complex comprising several genes or gene regions. To overcome this limitation, we performed an extended genetic association study analyzing 17 serotonergic ( SLC6A4, HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR6, MAOA, TPH1, TPH2 ) and dopaminergic genes ( SLC6A3, DRD2, DRD3, DRD4, COMT, MAOA, TH, DBH ), which have been previously reported to be implicated with personality traits.
One hundred and ninety-five single nucleotide polymorphisms (SNPs) within these genes were genotyped with the Illumina BeadChip technology (HumanHap300, Human-1) in a sample of 366 mentally healthy Caucasians. Additionally, we tried to replicate our results in an independent sample of further 335 Caucasians. Personality traits in both samples were assessed with the German version of Cloninger's Tridimensional Personality Questionnaire.
From 30 SNPs showing associations at a nominal level of significance, two intronic SNPs, rs2770296 and rs927544, both located in the HTR2A gene, withstood correction for multiple testing. These SNPs were associated with the personality trait novelty seeking . The effect of rs927544 could be replicated for the novelty seeking subscale extravagance , and the same SNP was also associated with extravagance inthe combined samples.
Our results show that HTR2A polymorphisms modulate facets of novelty seeking behaviour in healthy adults suggesting that serotonergic neurotransmission is involved in this phenotype.     

Ethnic Differences in Subcutaneous Adiposity and Waist Girth in Children and Adolescents

The purpose of this study was to examine ethnic differences in adiposity as measured by sum of skinfolds (SKF) and waist circumference (WC) in children and adolescents, after statistical adjustment for the BMI and age. A cross sectional sample of 3,218 (55% white, 49% male) children and adolescents aged 5–18 years who participated in the Bogalusa Heart Study (1992–1994) were included in these analyses. Sex‐specific ANOVAs, adjusted for BMI and age, for each 2‐year age group compared measures of adiposity (SKF and WC) between ethnic groups. No significant differences in the proportions of children and adolescents who were overweight and obese by ethnicity or sex were found. Mean SKF in normal weight (P < 0.0001) and overweight (P < 0.0001) categories was higher for white than black children of both sexes. Across most age categories, white boys and girls had significantly higher SKF than black boys and girls, respectively (P ≤ 0.05). Across most age categories, white boys had significantly higher WC than black boys (P ≤ 0.05) with no difference in the girls, when adjusted for BMI and age. Measures of adiposity in childhood and adolescence were significantly higher in white children compared to black children, when adjusted for BMI and age. Throughout childhood and adolescence, white boys and girls had higher SKF and white boys had higher WC. Differences in adiposity between ethnic groups should be considered in disease risk assessment and stratification as they are observed even for a given BMI level.     

Utility of Childhood BMI in the Prediction of Adulthood Disease: Comparison of National and International References

Objective: To determine whether the U.S. Centers for Disease Control and Prevention (CDC; CDC Reference) or International Obesity Task Force (IOTF; IOTF Reference) BMI cut‐off points for classifying adiposity status in children are more effective at predicting future health risk. Research Methods and Procedures: The sample (N = 1709) included 4‐ to 15‐year‐old (at baseline) boys and girls from the Bogalusa Heart Study. Overweight and obesity status were determined using both the CDC Reference and IOTF Reference BMI cut‐off points at baseline. The ability of childhood overweight and obesity, determined from the two BMI classification systems, to predict obesity and metabolic disorders in young adulthood (after a 13‐ to 24‐year follow‐up) was then compared. Results: Independently of the classification system employed to determine adiposity based on childhood BMI, the odds of being obese and having all of the metabolic disorders in young adulthood were significantly (p < 0.05) higher in the overweight and obese groups by comparison with the nonoverweight groups. Childhood overweight and obesity, determined by both the CDC Reference and IOTF Reference, had a low sensitivity and a high specificity for predicting obesity and metabolic disorders in young adulthood. Overweight and obesity as determined by the CDC Reference were slightly more sensitive and slightly less specific than the corresponding values based on the IOTF Reference. Discussion: Overweight and obesity during childhood, as determined by both the CDC and IOTF BMI cut‐off points, are strong predictors of obesity and coronary heart disease risk factors in young adulthood. The differences in the predictive capacity of the CDC Reference and IOTF Reference are, however, minimal.     

Genetic Effects on Longitudinal Changes from Healthy to Adverse Weight and Metabolic Status — The HUNT Study

IntroductionThe complexity of obesity and onset and susceptibility of cardio-metabolic disorders are still poorly understood and is addressed here through studies of genetic influence on weight gain and increased metabolic risk longitudinally.Subjects/MethodsTwenty seven previously identified obesity, eating disorder or metabolic risk susceptibility SNPs were tested for association with weight or metabolically related traits longitudinally in 3999 adults participating both in the HUNT2 (1995–97) and HUNT3 (2006–08) surveys. Regression analyses were performed with changes from normal weight to overweight/obesity or from metabolically healthy to adverse developments with regards to blood pressure, glucose, HDL cholesterol, triglycerides or metabolic syndrome as outcomes. Additionally, a sub-sample of 1380 adolescents was included for testing association of nine SNPs with longitudinal weight gain into young adulthood.ResultsThe most substantial effect on BMI-based weight gain from normal to overweight/obesity in adults was observed for the DRD2 variant (rs6277)(OR: 0.79, 95% CI: 0.69–0.90, P = 3.9x10^-4, adj. P = 0.015). DRD2 was not associated with BMI on a cross-sectional level. In the adolescent sample, FTO (rs1121980) was associated with change to overweight at adulthood in the combined male-female sample (OR: 1.27, 95% CI: 1.09–1.49, P = 3.0x10^-3, adj. P = 0.019) and in females (OR: 1.53, 95% CI: 1.23–1.91, P = 1.8x10^-4, adj. P = 0.003). When testing for association to longitudinal adverse developments with regard to blood pressure, blood lipids and glucose, only rs964184 (ZNF259/APOA5) was significantly associated to unfavourable triglyceride changes (OR: 1.66, 95% CI: 1.36–2.03, P = 5.7x10^-7, adj. P = 0.001). Pleiotropic effects on metabolic traits, however, were observed for several genetic loci cross-sectionally, ZNF259/APOA5, LPL and GRB14 being the most important.Conclusions DRD2 exhibits effects on weight gain from normal weight to overweight/obesity in adults, while, FTO is associated to weight gain from adolescence to young adulthood. Unhealthy longitudinal triglyceride development is strongly affected by ZNF259/APOA. Our main finding, linking the DRD2 variant directly to the longitudinal weight gain observed, has not previously been identified. It suggests a genetic pre-disposition involving the dopaminergic signalling pathways known to play a role in food reward and satiety linked mechanisms.     

Overweight in Childhood,Adolescence and Adulthood and Cardiovascular Risk in Later Life: Pooled Analysis of Three British Birth Cohorts

Background

Overweight and obesity in adulthood are established risk factors for adverse cardiovascular outcomes, but the contribution of overweight in childhood to later cardiovascular risk is less clear. Evidence for a direct effect of childhood overweight would highlight early life as an important target for cardiovascular disease prevention. The aim of this study was to assess whether overweight and obesity in childhood and adolescence contribute to excess cardiovascular risk in adults.

Methods and findings

Data from three British birth cohorts, born in 1946, 1958 and 1970, were pooled for analysis (n = 11,447). Individuals were categorised, based on body mass index (BMI), as being of normal weight or overweight/obese in childhood, adolescence and adulthood. Eight patterns of overweight were defined according to weight status at these three stages. Logistic regression models were fitted to assess the associations of patterns of overweight with self-reported type 2 diabetes, hypertension, and coronary heart disease (CHD) in adulthood (34–53 years). Compared to cohort members who were never overweight, those who were obese in adulthood had increased risk of all outcomes. For type 2 diabetes, the odds ratio was higher for obese adults who were also overweight or obese in childhood and adolescence (OR 12.6; 95% CI 6.6 to 24.0) than for those who were obese in adulthood only (OR 5.5; 95% CI 3.4 to 8.8). There was no such effect of child or adolescent overweight on hypertension. For CHD, there was weak evidence of increased risk among those with overweight in childhood. The main limitations of this study concern the use of self-reported outcomes and the generalisability of findings to contemporary child populations.

Conclusions

Type 2 diabetes and to a lesser extent CHD risk may be affected by overweight at all stages of life, while hypertension risk is associated more strongly with weight status in adulthood.     

Short allele of serotonin transporter gene promoter is a risk factor for obesity in adolescents

Obesity and hypertension are increasing medical problems in adolescents. Serotonin transporter (5-HTT) is involved in mood and eating disturbances. Encoded by the gene SLC6A4, the promoter shows functional insertion/deletion alleles: long (L) and short (S). Because individuals who are carriers for the short version are known to be at risk for higher levels of anxiety, we hypothesized that this variant may be associated with overweight. Data and blood samples were collected from 172 adolescents out of a cross-sectional, population-based study of 934 high school students. To replicate the findings, we also included 119 outpatients from the Nutrition and Diabetes Section of the Children's County Hospital. We found that the S allele was associated with overweight (BMI > 85th percentile), being a risk factor for overweight independently of sex, age, and hypertension [odds ratio (OR): 1.85; 95% confidence interval (CI): 1.13, 3.05; p < 0.02]. Additionally, in the outpatient study, compared with the homozygous LL subjects, S allele carriers showed a higher BMI z-score (1.47 +/- 1.09 vs. 0.51 +/- 1.4; p < 0.002) and were more frequent in overweight children. In conclusion, the S allele of the SLC6A4 promoter variant is associated with overweight being an independent genetic risk factor for obesity.     

Childhood Behavioral Problems Predict Young Adults' BMI and Obesity: Evidence From a Birth Cohort Stud

We examined whether behavioral problems in childhood and adolescence are associated with young adults' BMI and obesity, and tested whether childhood behavioral problems have a greater impact on young adults' obesity than adolescent behavioral problems. The data were from the Mater‐University of Queensland Study of Pregnancy (MUSP) and Its Outcomes, a population‐based birth cohort study commenced in Brisbane, Australia, in 1981. A subsample of 2,278 children for whom we had prospective information on their behavioral problems at ages 5 and 14 and measured BMI, and its categories (normal, overweight, and obese) at age 21 was chosen. Young adults who experienced behavioral problems at ages 5 or 14 had a greater average BMI and were more likely to be obese compared to young adults without behavioral problems at both ages. The childhood onset group was at greater risk of becoming obese by age 21 compared to the adolescent onset group (P = 0.04). These associations remained consistent after adjusting for a variety of potential covariates including maternal characteristics (i.e., demographics and life style), child dietary patterns, family meals, television (TV) watching, and participation in sports and exercise at 14 years. Childhood as well as persistent behavioral problems during childhood and adolescence predicts young adults' BMI and obesity. Although further studies are needed to confirm this association, there is a need for close monitoring of children presenting with behavioral problems.     

Socioeconomic position at different stages of the life course and its influence on body weight and weight gain in adulthood: a longitudinal study with 13-year follow-up

Socioeconomic inequalities in body weight have been demonstrated in numerous cross-sectional studies; however, little research has investigated these inequalities from a life course and longitudinal perspective. We examined the association between child- and adulthood socioeconomic position (SEP) and BMI and overweight/obesity in 1991 (baseline) and changes in BMI and the prevalence of overweight and obesity between 1991 and 2004. Data from the 1991 and 2004 waves of the longitudinal Dutch GLOBE study were used. Participants (n = 1,465) were aged 40-60 years at baseline. BMI was calculated from self-reported height and weight collected by postal questionnaire. Retrospective recall of father's occupation was used as childhood socioeconomic indicator, and adulthood SEP was measured by the occupation of the main income earner of the household. The findings showed that among women, childhood SEP exerted a greater influence on body weight than SEP in adulthood: at baseline, women from disadvantaged backgrounds in childhood had a higher BMI and were more likely to be overweight or obese, and they gained significantly more weight between baseline and follow-up. In contrast, adult SEP had a greater impact than childhood circumstances on men's body weight: those from disadvantaged households had a higher mean BMI and were more likely to be overweight or obese at baseline, and they gained significantly more weight between 1991 and 2004. The findings suggest that exposure to disadvantaged circumstances at critically important periods of the life course is associated with body weight and weight gain in adulthood. Importantly, these etiologically relevant periods differ for men and women, suggesting gender-specific pathways to socioeconomic inequalities in body weight in adulthood.     

Obesity-Susceptibility Loci and Their Influence on Adiposity-Related Traits in Transition from Adolescence to Adulthood - The HUNT Study

Introduction

Obesity-susceptibility loci have been related to adiposity traits in adults and may affect body fat estimates in adolescence. There are indications that different sets of obesity-susceptibility loci influence level of and change in obesity-related traits from adolescence to adulthood.

Objectives

To investigate whether previously reported obesity-susceptible loci in adults influence adiposity traits in adolescence and change in BMI and waist circumference (WC) from adolescence into young adulthood. We also examined whether physical activity modifies the effects of these genetic loci on adiposity-related traits.

Methods

Nine obesity-susceptibility variants were genotyped in 1 643 adolescents (13–19 years old) from the HUNT study, Norway, who were followed-up into young adulthood. Lifestyle was assessed using questionnaires and anthropometric measurements were taken. The effects of genetic variants individually and combined in a genetic predisposition score (GPS) on obesity-related traits were studied cross-sectionally and longitudinally. A modifying effect of physical activity was tested.

Results

The GPS was significantly associated to BMI (B: 0.046 SD/allele [0.020, 0.073], p = 0.001) in adolescence and in young adulthood (B: 0.041 SD/allele [0.015, 0.067], p = 0.002) as it was to waist circumference (WC). The GPS was not associated to change in BMI (p = 0.762) or WC (p = 0.726). We found no significant interaction effect between the GPS and physical activity.

Conclusions

Our observations suggest that obesity-susceptibility loci established in adults affect BMI and WC already in adolescence. However, an association with change in adiposity-related traits from adolescence to adulthood could not be verified for these loci. Neither could an attenuating effect of physical activity on the association between the obesity-susceptibility genes and body fat estimates be revealed.     

Physical inactivity and obesity: a vicious circle

Objective: Physical activity (PA) begins to decline in adolescence with a concomitant increase in weight. We hypothesized that a vicious circle may arise between decreasing PA and weight gain from adolescence to early adulthood. Methods and Procedures: PA and self‐perceived physical fitness assessed in adolescents (16–18 years of age) were used to predict the development of obesity (BMI ≥30 kg/m²) and abdominal obesity (waist ≥88 cm in females and ≥102 cm in males) at age 25 in 4,240 twin individuals (90% of twins born in Finland, 1975–1979). Ten 25‐year‐old monozygotic (MZ) twin pairs who were discordant for obesity (with a 16 kg weight difference) were then carefully evaluated for current PA (using a triaxial accelerometer), total energy expenditure (TEE, assessed by means of the doubly labeled water (DLW) method), and basal metabolic rate (BMR, assessed by indirect calorimetry). Results: Physical inactivity in adolescence strongly predicted the risk for obesity (odds ratio (OR) 3.9, 95% confidence interval (CI) 1.4–10.9) and abdominal obesity (4.8, 1.9–12.0) at age 25, even after adjusting for baseline and current BMI. Poor physical fitness in adolescence also increased the risk for overall obesity (5.1, 2.0–12.7) and abdominal obesity (3.2, 1.5–6.7) in adulthood. Physical inactivity was both causative and secondary to the development of obesity discordance in the MZ pairs. TEE did not differ between the MZ co‐twins. PA was lower whereas BMR was higher in the obese co‐twins. Discussion: Physical inactivity in adolescence strongly and independently predicts total (and especially) abdominal obesity in young adulthood, favoring the development of a self‐perpetuating vicious circle of obesity and physical inactivity. Physical activity should therefore be seriously recommended for obesity prevention in the young.     

Development of Health‐Related Waist Circumference Thresholds Within BMI Categories

Objective: To develop and cross‐validate waist circumference (WC) thresholds within BMI categories. The utility of the derived values was compared with the single WC thresholds (women, 88 cm; men, 102 cm) recommended by NIH and Health Canada. Research Methods and Procedures: The sample included adults classified as normal weight (BMI = 18.5 to 24.9), overweight (BMI = 25 to 29.9), obese I (BMI = 30 to 34.9), and obese II+ (BMI ≥ 35) from the Third U.S. National Health and Nutrition Examination Survey (NHANES III; n = 11, 968) and the Canadian Heart Health Surveys (CHHS; n = 6286). Receiver operating characteristic curves were used to determine the optimal WC thresholds that predicted high risk of coronary events (top quintile of Framingham scores) within BMI categories using the NHANES III. The BMI‐specific WC thresholds were cross‐validated using the CHHS. Results: The optimal WC thresholds increased across BMI categories from 87 to 124 cm in men and from 79 to 115 cm in women. The validation study indicated improved sensitivity and specificity with the BMI‐specific WC thresholds compared with the single thresholds. Discussion: Compared with the recommended WC thresholds, the BMI‐specific values improved the identification of health risk. In normal weight, overweight, obese I, and obese II+ patients, WC cut‐offs of 90, 100, 110, and 125 cm in men and 80, 90, 105, and 115 cm in women, respectively, can be used to identify those at increased risk.