FTO influences on longitudinal BMI over childhood and adulthood and modulation on relationship between birth weight and longitudinal BMI

SNP rs9939609 within the fat mass and obesity associated gene (FTO) is strongly associated with adult body mass index (BMI). However, influences of FTO on longitudinal BMI change from childhood to adulthood have not been examined. Knowledge is limited on FTO, modulating the association between birth weight and longitudinal change of BMI. This longitudinal study examined SNPs of FTO in 658 white subjects from childhood (3–17 years) to adulthood (18–45 years). No significant associations of FTO SNPs with either birth weight or longitudinal BMI over childhood were noted after multiple-test adjustment. However, three SNPs (rs9939609, rs17820875 and rs860713) with different inheritance patterns were identified to be associated with longitudinal BMI over adulthood after Bonferroni adjustment (P = 5.3 × 10⁻⁵, 2.0 × 10⁻⁴ and 0.001). In addition, interactions were discovered between birth weight and SNPs of rs17820875 (P = 0.001) and rs860713 (0.002). A negative association between birth weight and adult BMI were found in risk genotype AG of rs17820875 and GG of rs860713 in contrast to positive associations in other genotypes. These findings led to the conclusion that lower birth weight predisposes to higher adult BMI depending on FTO risk genotypes. Our studies underscore the importance of FTO influences on obesity and provide insights into the evolution of the long-term burden of obesity.     

The FTO gene and obesity in a large Eastern European population sample: the HAPIEE study

Variants in the FTO (oxoglutarate-dependent nucleic acid demethylase) gene have been associated with the BMI determination in Western European and North American populations. To widen the geographical coverage of the FTO studies, we have analyzed the association between the FTO gene variant rs17817449 (G>C) and obesity in a Slavic Eastern European population. A total of 3,079 males and 3,602 females 45-69 years old were randomly selected from population registers of seven Czech cities. We examined three indices of obesity: BMI (kg/m(2)), waist circumference, and waist-to-hip ratio (WHR). The FTO rs17817449 variant was significantly associated with BMI both in males (GG 28.7 +/- 4.1; GT 28.3 +/- 3.9; TT 28.0 +/- 3.9; P = 0.003) and females (GG 28.7 +/- 5.2; GT 28.2 +/- 5.1; TT 27.2 +/- 4.9; P < 0.001); the associations were not affected by adjustment for age, smoking, socioeconomic status, and physical activity. The FTO variant was also associated with waist circumference (difference between GG and TT was 1.1 cm (P = 0.043) in men and 2.4 cm (P < 0.001) in women) but this relationship disappeared after adjustment for BMI. Similarly, BMI explained the weak association of FTO with WHR and C-reactive protein. FTO was not associated with plasma total and high-density lipoprotein cholesterol, triglycerides, blood glucose, and blood pressure. These results confirm that in a Slavic population the FTO variant is strongly associated with BMI but not with other risk factors.     

Responses to FTO genetic test feedback for obesity in a sample of overweight adults: a qualitative analysis

Current evidence indicates that genetic testing for obesity risk has limited affective or behavioral impact, but few studies have explored the effects among individuals who self-identify as having weight problems. Here, we report findings from in-depth telephone interviews with seven overweight or obese volunteers who were genotyped for one weight-related gene (FTO), which may offer interesting insights into motivations to seek out genetic testing and immediate reactions to it. All participants had a BMI > 25. The gene test identified one participant as homozygous for the ‘higher-risk’ variant (AA), three heterozygous (AT), and three homozygous for the ‘lower-risk’ variant (TT) of FTO. All participants said they took part to find an explanation for their personal struggle with weight control. Those with one or two higher-risk variants experienced relief and saw the result as confirming their private assumption that they were susceptible to weight gain for reasons perceived as ‘external’ to them. However, at the same time, they described themselves as more motivated to overcome their genetic predisposition. Those with lower-risk variants reported brief disappointment, but then focused on alternative explanations, reinforcing the multifactorial nature of obesity. Despite objectively low ‘information value,’ all individuals derived some ‘personal’ benefit from FTO genetic test feedback. However, improving education about the multifactorial nature of complex conditions is important to decrease polarized thinking and associated genetic determinism and stigma to derive the greatest benefits of novel genetic technologies for individuals and their health.     

Low numeracy skills are associated with higher BMI

Low numeracy skills and obesity are both common. Numeracy skills are used in healthy weight management to monitor caloric intake. The relationship between obesity and numeracy skills in adult primary care patients is unknown. A cross-sectional study enrolled adult, English-speaking primary care patients. BMI was assessed by self-report; numeracy and literacy skills were measured with the Wide Range Achievement Test, 3rd Edition (WRAT-3) and the Rapid Estimate of Adult Literacy in Medicine (REALM), respectively. The relationship between numeracy and BMI was described with Spearman's rank correlation and linear regression analyses. In 160 patients, the mean (s.d.) age was 46 (16) years, 66% were white, 70% were female, and 91% completed high school. The mean BMI was 30.5 (8.3) kg/m(2). Less than 9th grade numeracy skills were found in 66% of the participants. Participants with numeracy skills <9th grade had a mean BMI of 31.8 (9.0) whereas those with numeracy skills > or =9th grade had a mean BMI of 27.9 (6.0), P = 0.008. Numeracy was negatively and significantly correlated with BMI (rho = -0.26, P = 0.001). This correlation persisted after adjusting for age, sex, race, income, years of education, and literacy (beta coefficient = -0.14; P = 0.010). Literacy skills were not associated with BMI. We found a significant association between low numeracy skills and higher BMI in adult primary care patients. A causal relationship cannot be determined. However, numeracy may have important clinical implications in the design and implementation of healthy weight management interventions and should be further evaluated to determine the magnitude of its effect.     

Impact of physician BMI on obesity care and beliefs

Using a national cross-sectional survey of 500 primary care physicians conducted between 9 February and 1 March 2011, the objective of this study was to assess the impact of physician BMI on obesity care, physician self-efficacy, perceptions of role-modeling weight-related health behaviors, and perceptions of patient trust in weight loss advice. We found that physicians with normal BMI were more likely to engage their obese patients in weight loss discussions as compared to overweight/obese physicians (30% vs. 18%, P = 0.010). Physicians with normal BMI had greater confidence in their ability to provide diet (53% vs. 37%, P = 0.002) and exercise counseling (56% vs. 38%, P = 0.001) to their obese patients. A higher percentage of normal BMI physicians believed that overweight/obese patients would be less likely to trust weight loss advice from overweight/obese doctors (80% vs. 69%, P = 0.02). Physicians in the normal BMI category were more likely to believe that physicians should model healthy weight-related behaviors-maintaining a healthy weight (72% vs. 56%, P = 0.002) and exercising regularly (73% vs. 57%, P = 0.001). The probability of a physician recording an obesity diagnosis (93% vs. 7%, P < 0.001) or initiating a weight loss conversation (89% vs. 11%, P ≤ 0.001) with their obese patients was higher when the physicians' perception of the patients' body weight met or exceeded their own personal body weight. These results suggest that more normal weight physicians provided recommended obesity care to their patients and felt confident doing so.     

Association of the FTO gene with BMI

Variants in the FTO gene have been strongly associated with obesity in a very large sample (38,759) of diabetic and control subjects. To replicate these findings, the previously reported SNP in the FTO gene (rs9939609, T/A) was genotyped in 5,607 subjects from five different Utah studies. The studies included a random sample of the Utah population, families selected for aggregation of extreme thinness, families selected for severe obesity, a series of unrelated severe obesity subjects, and families participating in a 25-year longitudinal study of cardiovascular disease and aging. Results show a strong significant increase in the rs9939609 A allele frequency with increasing BMI (P < 0.0001). In the longitudinal study, FTO genotypes were significantly associated with BMI at a baseline exam, a 2(1/2)-year follow-up exam and a 25-year follow-up exam using an additive genetic model. The mean genotype difference in BMI ranged from 1.3 to 2.1 kg/m(2) across exams. The genotype difference in BMI means was established in youth, and at-risk subjects under age 20 at baseline had a significantly larger 25-year BMI increase (10.0 for A/A; 9.7 for A/T, and 8.5 kg/m(2) for T/T, P = 0.05). We conclude that the BMI increases associated with FTO genotypes begin in youth and are maintained throughout adulthood.     

Impact of variation in the FTO gene on whole body fat distribution, ectopic fat, and weight loss

Polymorphisms in the fat mass- and obesity-associated (FTO) gene have been identified to be associated with obesity and diabetes in large genome-wide association studies. We hypothesized that variation in the FTO gene has an impact on whole body fat distribution and insulin sensitivity, and influences weight change during lifestyle intervention. To test this hypothesis, we genotyped 1,466 German subjects, with increased risk for type 2 diabetes, for single-nucleotide polymorphism rs8050136 in the FTO gene and estimated glucose tolerance and insulin sensitivity from an oral glucose tolerance test (OGTT). Distribution of fat depots was quantified using whole body magnetic resonance (MR) imaging and spectroscopy in 298 subjects. Two-hundred and four subjects participated in a lifestyle intervention program and were examined after a follow-up of 9 months. In the cross-sectional analysis, the A allele of rs8050136 in FTO was associated with a higher BMI, body fat, and lean body mass (all P < 0.001). There was a significant effect of variation in the FTO gene on subcutaneous fat (P < or = 0.05) and a trend for liver fat content, nonvisceral adipose tissue, and visceral fat (all P < or = 0.1). However, the single-nucleotide polymorphism was not associated with insulin sensitivity or secretion independent of BMI (all P > 0.05). During lifestyle intervention, there was also no influence of the FTO polymorphism on changes in body weight or fat distribution. In conclusion, despite an association with BMI and whole body fat distribution, variation in the FTO locus has no effect on the success of a lifestyle intervention program.     

Comparison of measured and parents' reported height and weight in children and adolescents

The objectives of this study were to (i) compare parent-reported height and weight to measured height and weight in children between ages 2 and 17 years, (ii) investigate correlations between magnitude of error of parent-reported data or refusal to estimate height and weight with gender, race/ethnicity, child's age, and age-specific BMI z-score, and (iii) determine sensitivity and specificity of identifying obese youth based on parent-reported data. The authors studied 1,430 consecutive outpatients between ages 2 and 17 years at an outpatient orthopedic clinic. At the initial visit, parents completed a questionnaire including their child's height and weight; height and weight were then measured. Mean height error was very small, with slight overestimation in boys and underestimation in girls. Mean weight error increased with age (P < 0.001), and girls had a larger mean weight error (1.29 kg, 95% confidence interval (CI): 0.65, 1.45) than boys (0.85 kg, 95% CI: 0.8: 0.58, 1.12). Mean weight error also increased with age-specific BMI z-score (r = 0.32, P < 0.001). Correlation between weight error and age-specific BMI z-score was higher among black children (r = 0.45, P < 0.001) than among Hispanic children (r = 0.37, P < 0.001) and was lowest among white children (r = 0.29, P < 0.001). Refusal or inability to estimate weight did not correlate with age-specific BMI z-score. Twenty-one percent of children who were obese would not be identified by using parent-reported data to calculate the BMI.     

Association of the FTO rs9939609 polymorphism with obesity in Roma/Gypsy population

The rs9939609 SNP located in the first intron of the fat mass and obesity associated gene (FTO) has been found to be associated with common obesity mainly in populations of European descent. The Roma/Gypsy population as an ethnic minority of Asian Indian origin is well known for its adverse health status with a high prevalence of obesity. The main aim of this study was to examine the contribution of the rs9939609 FTO polymorphism to the high prevalence of obesity in the Roma/Gypsy population. Following a number of anthropometric measurements, the FTO rs9939609 polymorphism was genotyped in 312 Roma/Gypsy individuals. We observed significant differences in body mass index (BMI), waist circumference, and waist-to-hip ratio between different genotypes (P = 0.003, P = 0.012, and P = 0.03, respectively). The waist circumference in the subjects with AA genotype was about 7.1 cm larger than in those with TT genotypes (P = 0.005). However, the strongest association of minor allele A of the rs9939609 FTO polymorphism was found with BMI (odds ratio, 1.55; 95% confidence interval, 1.129-2.128; P = 0.007), even after adjusting for age, sex, and smoking status. This study provides the first report of allele and genotype frequencies for the rs9939609 polymorphism and also the first evidence of the association of the FTO variant with obesity in the Roma/Gypsy population.     

The FTO gene is associated with adulthood obesity in the Mexican population

Common polymorphisms in the fat mass and obesity-associated gene (FTO) have shown strong association with obesity in several populations. In the present study, we explored the association of FTO gene polymorphisms with obesity and other biochemical parameters in the Mexican population. We also assessed FTO gene expression levels in adipose tissue of obese and nonobese individuals. The study comprised 788 unrelated Mexican-Mestizo individuals and 31 subcutaneous fat tissue biopsies from lean and obese women. FTO single-nucleotide polymorphisms (SNPs) rs9939609, rs1421085, and rs17817449 were associated with obesity, particularly with class III obesity, under both additive and dominant models (P = 0.0000004 and 0.000008, respectively). These associations remained significant after adjusting for admixture (P = 0.000003 and 0.00009, respectively). Moreover, risk alleles showed a nominal association with lower insulin levels and homeostasis model assessment of B-cell function (HOMA-B), and with higher homeostasis model assessment of insulin sensitivity (HOMA-S) only in nonobese individuals (P (dom) = 0.031, 0.023, and 0.049, respectively). FTO mRNA levels were significantly higher in subcutaneous fat tissue of class III obese individuals than in lean individuals (P = 0.043). Risk alleles were significantly associated with higher FTO expression in the class III obesity group (P = 0.047). In conclusion, FTO is a major risk factor for obesity (particularly class III) in the Mexican-Mestizo population, and is upregulated in subcutaneous fat tissue of obese individuals.     

Metabolic predictors of inflammation, adhesion, and coagulability in healthy younger-aged adults

Elevated levels of inflammatory biomarkers are associated with the pathophysiology of cardiovascular diseases and are predictors of cardiovascular events. The objective of this study was to determine the unique contributions of metabolic factors as predictors of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)), adhesion (soluble intercellular adhesion molecule-1 (sICAM-1)), and coagulation (D-dimer) in healthy younger-aged adults. Participants were 83 women and 92 men (mean age 30.04 years, s.d. +/- 4.8, range 22-39) of normal weight to moderate obese weight (mean BMI 24.4 kg/m(2), s.d. +/- 3.35, range 17-32). The primary data analytical approaches included Pearson correlation and multiple linear regression. Circulating levels of CRP, IL-6, sICAM-1, and D-dimer were determined in plasma. Higher levels of CRP were independently associated with higher BMI, a greater waist-to-hip ratio, female gender, and higher triglycerides (P < 0.001). Higher IL-6 levels were independently associated with a greater waist-to-hip ratio (P < 0.01). Higher levels of sICAM-1 were independently associated with higher BMI, higher triglycerides, and lower insulin resistance (P < 0.001). Higher D-dimer levels were independently associated with higher BMI and being female (P < 0.001). Having a higher BMI was most consistently associated with elevated biomarkers of inflammation, adhesion, and coagulation in this sample of healthy younger-aged adults, although female gender, insulin resistance, and lipid levels were also related to the biomarkers. The findings provide insight into the adverse cardiovascular risk associated with elevated body weight in younger adults.     

Increasing heritability of BMI and stronger associations with the FTO gene over childhood

The growing evidence of health risks associated with the rise in childhood obesity adds to the urgency of understanding the determinants of BMI. Twin analyses on repeated assessments of BMI in a longitudinal sample of >7,000 children indicated that the genetic influence on BMI becomes progressively stronger, with heritability increasing from 0.48 at age 4 to 0.78 at age 11. In the same large twin sample, the association between a common variant in the FTO gene and BMI increased in parallel with the rise in heritability, going from R(2) < 0.001 at age 4 to R(2) = 0.01 at age 11. These findings suggest that expression of FTO may become stronger throughout childhood. Increases in heritability may also be due to children increasingly selecting environments correlated with their genetic propensities.     

Early hypothalamic FTO overexpression in response to maternal obesity--potential contribution to postweaning hyperphagia

Background

Intrauterine and postnatal overnutrition program hyperphagia, adiposity and glucose intolerance in offspring. Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene have been linked to increased risk of obesity. FTO is highly expressed in hypothalamic regions critical for energy balance and hyperphagic phenotypes were linked with FTO SNPs. As nutrition during fetal development can influence the expression of genes involved in metabolic function, we investigated the impact of maternal obesity on FTO.

Methods

Female Sprague Dawley rats were exposed to chow or high fat diet (HFD) for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1 (PND1), some litters were adjusted to 3 pups (vs. 12 control) to induce postnatal overnutrition. At PND20, rats were weaned onto chow or HFD for 15 weeks. FTO mRNA expression in the hypothalamus and liver, as well as hepatic markers of lipid metabolism were measured.

Results

At weaning, hypothalamic FTO mRNA expression was increased significantly in offspring of obese mothers and FTO was correlated with both visceral and epididymal fat mass (P<0.05); body weight approached significance (P = 0.07). Hepatic FTO and Fatty Acid Synthase mRNA expression were decreased by maternal obesity. At 18 weeks, FTO mRNA expression did not differ between groups; however body weight was significantly correlated with hypothalamic FTO. Postnatal HFD feeding significantly reduced hepatic Carnitine Palmitoyltransferase-1a but did not affect the expression of other hepatic markers investigated. FTO was not affected by chronic HFD feeding.

Significance

Maternal obesity significantly impacted FTO expression in both hypothalamus and liver at weaning. Early overexpression of hypothalamic FTO correlated with increased adiposity and later food intake of siblings exposed to HFD suggesting upregulation of FTO may contribute to subsequent hyperphagia, in line with some human data. No effect of maternal obesity was observed on FTO in adulthood.     

Common SNPs in FTO Gene Are Associated with Obesity Related Anthropometric Traits in an Island Population from the Eastern Adriatic Coast of Croatia

Background

Multiple studies have provided compelling evidence that the FTO gene variants are associated with obesity measures. The objective of the study was to investigate whether FTO variants are associated with a broad range of obesity related anthropometric traits in an island population.

Methodology/Principal Findings

We examined genetic association between 29 FTO SNPs and a comprehensive set of anthropometric traits in 843 unrelated individuals from an island population in the eastern Adriatic coast of Croatia. The traits include 11 anthropometrics (height, weight, waist circumference, hip circumference, bicondilar upper arm width, upper arm circumference, and biceps, triceps, subscapular, suprailiac and abdominal skin-fold thicknesses) and two derived measures (BMI and WHR). Using single locus score tests, 15 common SNPs were found to be significantly associated with “body fatness” measures such as weight, BMI, hip and waist circumferences with P-values ranging from 0.0004 to 0.01. Similar but less significant associations were also observed between these markers and bicondilar upper arm width and upper arm circumference. Most of these significant findings could be explained by a mediating effect of “body fatness”. However, one unique association signal between upper arm width and rs16952517 (P-value = 0.00156) could not be explained by this mediating effect. In addition, using a principle component analysis and conditional association tests adjusted for “body fatness”, two novel association signals were identified between upper arm circumference and rs11075986 (P-value = 0.00211) and rs16945088 (P-value = 0.00203).

Conclusions/Significance

The current study confirmed the association of common variants of FTO gene with “body fatness” measures in an isolated island population. We also observed evidence of pleiotropic effects of FTO gene on fat-free mass, such as frame size and muscle mass assessed by bicondilar upper arm width and upper arm circumference respectively and these pleiotropic effects might be influenced by variants that are different from the ones associated with “body fatness”.     

Loss of control is central to psychological disturbance associated with binge eating disorder

Objective: Binge eating disorder (BED) is positively associated with obesity and psychological distress, yet the behavioral features of BED that drive these associations are largely unexplored. The primary aim of this study was to investigate which core behavioral features of binge eating are most strongly related to psychological disturbance. Methods and Procedures: A cross‐sectional study involved 180 bariatric surgery candidates, 93 members of a non‐surgical weight loss support group, and 158 general community respondents (81 men/350 women, mean age 45.8 ± 13.3, mean BMI 34.8 ± 10.8, BMI range 17.7–66.7). Validated questionnaires assessed BED and binge eating, symptoms of depression, appearance dissatisfaction (AD), quality of life (QoL) and eating‐related behaviors. Features of binge eating were confirmed by interview. BMI was determined by clinical assessment and self‐report. Results: The loss of control (LOC) over eating, that is, being unable to stop eating or control what or how much was consumed was most closely related to psychological markers of distress common in BED. In particular, those who experienced severe emotional disturbance due to feelings of LOC reported higher symptoms of depression (P < 0.001), AD (P = 0.009), and poorer mental health–related QoL (P = 0.027). Discussion: Persons who report subjective binge episodes or do not meet BED frequency criteria for objective binge episodes may still be at elevated risk of psychological disturbance and benefit from clinical intervention. Feelings of LOC could drive binge eaters to seek bariatric surgery in an attempt to gain control over body weight and psychologically disturbing eating behavior.     

Higher Body Mass Index Increases the Risk for Biopsy-Mediated Detection of Prostate Cancer in Chinese Men

Objective

To investigate the relationship between body mass index (BMI) and prostate cancer (PCa) risk at biopsy in Chinese men.

Patients and Methods

We retrospectively reviewed the records of 1,807 consecutive men who underwent initial multicore (≥10) prostate biopsy under transrectal ultrasound guidance between Dec 2004 and Feb 2014. BMI was categorised based on the Asian classification of obesity as follows: <18.5 (underweight), 18.5–22.9 (normal weight), 23–24.9 (overweight), 25–29.9 (moderately obese), and ≥30 kg/m2 (severely obese). The odds ratios (OR) of each BMI category for risk of PCa and high-grade prostate cancer (HGPCa, Gleason score ≥4+3) detection were estimated in crude, age-adjusted and multivariate-adjusted models. Prevalence ratios and accuracies of PSA predicted PCa were also estimated across BMI groups.

Results

In total, PCa was detected by biopsy in 750 (45.4%) men, and HGPCa was detected in 419 (25.4%) men. Compared with men of normal weight, underweight men and obese men were older and had higher prostate specific antigen levels. The risk of overall PCa detection via biopsy presented an obvious U-shaped relationship with BMI in crude analysis. Overall, 50.0%, 37.4%, 45.6% 54.4% and 74.1% of the men in the underweight, normal weight, overweight, moderately obese and severely obese groups, respectively, were diagnosed with PCa via biopsy. In multivariate analysis, obesity was significantly correlated with a higher risk of PCa detection (OR = 1.17, 95%CI 1.10–1.25, P<0.001). However, higher BMI was not correlated with HGPCa detection (OR = 1.03, 95%CI 0.97–1.09, P = 0.29). There were no significant differences in the accuracy of using PSA to predict PCa or HGPCa detection across different BMI categories.

Conclusion

Obesity was associated with higher risk of PCa detection in the present Chinese biopsy population. No significant association was detected between obesity and HGPCa.     

High leptin/adiponectin ratio and serum triglycerides are associated with an "at-risk" phenotype in young severely obese patients

"At-risk" severely obese subjects are characterized by insulin resistance, and higher visceral fat and plasma lipid levels compared with metabolically healthy obese (MHO) subjects, although both groups have a high BMI and fat mass. The aim of this study was to measure several serum adipokines and gastrointestinal hormones in a young severely obese population from Southern Italy to identify biochemical markers of the "at-risk" insulin-resistant obese profile. We studied 160 unrelated white young adults (mean age = 25.2 years, mean BMI = 44.9 kg/m(2), 65% women) affected by obesity for at least 5 years. Serum concentrations of glucagon, ghrelin, gastric inhibitory peptide, glucagon like peptide-1, interleukin-6, tumor necrosis factor α, leptin, adiponectin, adipsin, and visfatin were measured. The leptin/adiponectin (L/A) ratio and fatty liver index (FLI) were calculated. We found a prevalence of 21.3% of MHO patients in our young severely obese patients. At univariate analysis, the "at-risk" group had higher mean levels of BMI (P < 0.0001), leptin (P = 0.039, men) and the L/A ratio (P = 0.003), and lower mean levels of visfatin (P = 0.026) than the MHO group. The L/A ratio, serum triglycerides, and male sex were significantly associated with "at-risk" obesity and accounted for 19.5% of insulin resistance at multivariate analysis. In conclusion, we demonstrate that a high serum L/A ratio and high levels of serum triglycerides may be markers of "at-risk" obesity, independent of waist circumference (WC) and BMI, in young severely obese population.     

Sleep duration and BMI in a sample of young adults

We examined the association between sleep duration and BMI in young adults, and, specifically, in possible gender differences. The population-based sample included 955 young men and 1051 young women (mean age = 25.3 years, s.d. = 1.7) who participated in Project EAT-III (Eating and Activity in Teens and Young Adults)-III. In 2008-2009, study participants completed a survey, on which they reported their weight, height, and typical bed and awakening times. Gender-specific regression models estimated cross-sectional associations between sleep duration and weight status, adjusting for age, race, SES, family structure, depressive symptoms, physical activity, and sedentary and dietary behaviors. In multivariable-adjusted linear regression models, an hour increase in sleep was associated with a -0.38 (-0.70, -0.048) BMI in men. Men who slept <7 h had a 1.4 unit higher mean BMI (27.9; 95% confidence interval (CI): 26.9, 28.9) than men who slept 7-9 h/day (26.5; 95% CI: 26.1, 27.0). Prevalence estimates of overweight (BMI ≥ 25) and obesity (BMI ≥ 30) were also inversely associated with sleep duration among men. Sleep duration was not associated with BMI, overweight, or obesity in women. Among women, but not men, there was a statistically significant positive association between trouble falling or staying asleep and mean BMI. Sleep may be an important modifiable risk factor for obesity, particularly in young adult men.