Future Weight Gain Research Articles

Serum metabolite profile associates with the development of metabolic co-morbidities in first-episode psychosis.

Psychotic patients are at high risk for developing obesity, metabolic syndrome and type 2 diabetes. These metabolic co-morbidities are hypothesized to be related to both treatment side effects as well as to metabolic changes occurring during the psychosis. Earlier metabolomics studies have shown that blood metabolite levels are predictive of insulin resistance and type 2 diabetes in the general population as well as sensitive to the effects of antipsychotics. In this study, we aimed to identify the metabolite profiles predicting future weight gain and other metabolic abnormalities in psychotic patients. We applied comprehensive metabolomics to investigate serum metabolite profiles in a prospective study setting in 36 first-episode psychosis patients during the first year of the antipsychotic treatment and 19 controls. While corroborating several earlier findings when comparing cases and controls and the effects of the antipsychotic medication, we also found that prospective weight gain in psychotic patients was associated with increased levels of triacylglycerols with low carbon number and double-bond count at baseline, that is, lipids known to be associated with increased liver fat. Our study suggests that metabolite profiles may be used to identify the psychotic patients most vulnerable to develop metabolic co-morbidities, and may point to a pharmacological approach to counteract the antipsychotic-induced weight gain.

Does basal metabolic rate predict weight gain?

Some previous studies have indicated that a low basal metabolic rate (BMR) is an independent predictor of future weight gain, but low rates of follow-up and highly select populations may limit the ability to generalize the results. We assessed whether adults with a low BMR gain more weight than do adults with a high BMR who are living in a typical Western environment. We extracted BMR, body-composition, demographic, and laboratory data from electronic databases of 757 volunteers who were participating in our research protocols at the Mayo Clinic between 1995 and 2012. Research study volunteers were always weight stable, had no acute illnesses and no confounding medication use, and were nonsmokers. The top and bottom 15th percentiles of BMR, adjusted for fat-free mass (FFM), fat mass, age, and sex, were identified. Follow-up electronic medical record system data were available for 163 subjects, which allowed us to determine their subsequent weight changes for ≥3 y (mean: ∼9.7 y). By definition, the BMR was different in the high-BMR group (2001 ± 317 kcal/d; n = 86) than in the low-BMR group (1510 ± 222 kcal/d; n = 77), but they were comparable with respect to age, body mass index, FFM, and fat mass. Rates of weight gain were not greater in the bottom BMR group (0.3 ± 1.0 kg/y) than in the top BMR group (0.5 ± 1.5 kg/y) (P = 0.17). Adults with low BMRs did not gain more weight than did adults with high BMRs, implying that habitual differences in food intake or activity counterbalance variations in BMR as a risk factor for weight gain in a typical Western population.

Low energy intake plus low energy expenditure (low energy flux), not energy surfeit, predicts future body fat gain

There is a paucity of studies that have prospectively tested the energy surfeit theory of obesity with the use of objectively estimated energy intake and energy expenditure in humans. An alternative theory is that homeostatic regulation of body weight is more effective when energy intake and expenditure are both high (high energy flux), implying that low energy flux should predict weight gain. We aimed to examine the predictive relations of energy balance and energy flux to future weight gain and tested whether results were replicable in 2 independent samples. Adolescents (n = 154) and college-aged women (n = 75) underwent 2-wk objective doubly labeled water, resting metabolic rate, and percentage of body fat measures at baseline. Percentage of body fat was measured annually for 3 y of follow-up for the adolescent sample and for 2 y of follow-up for the young adult sample. Low energy flux, but not energy surfeit, predicted future increases in body fat in both studies. Furthermore, high energy flux appeared to prevent fat gain in part because it was associated with a higher resting metabolic rate. Counter to the energy surfeit model of obesity, results suggest that increasing energy expenditure may be more effective for reducing body fat than caloric restriction, which is currently the treatment of choice for obesity. This trial was registered at clinicaltrials.gov as NCT02084836.

Impulse control and restrained eating among young women: Evidence for compensatory cortical activation during a chocolate-specific delayed discounting task

Theory and associated research indicate that people with elevated restrained eating (RE) scores have higher risk for binge eating, future bulimic symptom onset and weight gain. Previous imaging studies have suggested hyper-responsive reward brain area activation in response to food cues contributes to this risk but little is known about associated neural impulse control mechanisms, especially when considering links between depleted cognitive resources related to unsuccessful RE. Towards illuminating this issue, we used a chocolate-specific delayed discounting (DD) task to investigate relations between RE scores, behavior impulsivity, and corresponding neural impulse control correlates in a functional magnetic resonance imaging (fMRI) study of 27 young women. Specifically, participants were required to choose between more immediate, smaller versus delayed, larger hypothetical chocolate rewards following initial consumption of a chocolate. As predicted, RE scores were correlated positively with behavior impulse control levels. More critically, higher RE scores were associated with stronger activation in impulse control region, the dorsal-lateral prefrontal cortex (DLPFC) during the completion of difficult decision trials reflecting higher cognitive demands and resource depletion relative to easy decision trials. Exploratory analyses revealed a positive correlation between RE scores and activity in a reward system hub, the right striatum. Moreover, a positive correlation between left DLPFC and striatum activation was posited to reflect, in part, impulse control region compensation in response to stronger reward signal among women with RE elevations. Findings suggested impulse control lapses may contribute to difficulties in maintaining RE, particularly when cognitive demands are high.

Neural vulnerability factors that increase risk for future weight gain.

Theorists have proposed several neural vulnerability factors that may increase overeating and consequent weight gain. Early cross-sectional imaging studies could not determine whether aberrant neural responsivity was a precursor or consequence of overeating. However, recent prospective imaging studies examining predictors of future weight gain and response to obesity treatment, and repeated-measures imaging studies before and after weight gain and loss have advanced knowledge of etiologic processes and neural plasticity resulting from weight change. The present article reviews evidence from prospective studies using imaging and behavioral measures reflecting neural function, as well as randomized experiments with humans and animals that are consistent or inconsistent with 5 neural vulnerability theories for excessive weight gain. Extant data provide strong support for the incentive sensitization theory of obesity and moderate support for the reward surfeit theory, inhibitory control deficit theory, and dynamic vulnerability model of obesity, which attempted to synthesize the former theories into a single etiologic model. However, existing data provide only minimal support for the reward deficit theory. Findings are synthesized into a new working etiologic model that is based on current scientific knowledge. Important directions for future studies, which have the potential to support or refute this working etiologic model, are delineated. (PsycINFO Database Record

Parental Perception of Weight Status and Weight Gain Across Childhood.

Parents of children who are overweight often fail to accurately identify their child's weight status. Although these misperceptions are presumed to be a major public health concern, little research has examined whether parental perceptions of child weight status are protective against weight gain during childhood. Our objective was to examine whether parental perceptions of child weight status are associated with weight gain across childhood. Data from the Longitudinal Study of Australian Children were used to assess parental perceptions of child weight status and to examine changes in researcher measured child BMI z scores across childhood, from 4 to 13 years old. Participants included 3557 Australian children and their parents. Children whose parents perceived their weight as being "overweight," as opposed to "about the right weight," gained more weight (increase in BMI z score) from baseline to follow-up in all analyses. This finding did not depend on the actual weight of the child; the association between perceiving one's child as being overweight and future weight gain was similar among children whose parents accurately and inaccurately believed their child was overweight. Contrary to popular belief, parental identification of child overweight is not protective against further weight gain. Rather, it is associated with more weight gain across childhood. Further research is needed to understand how parental perceptions of child weight may counterintuitively contribute to obesity.

Abstract P125: Aerobic Exercise Training Reduces Postprandial Thermogenesis in Older Women

Introduction: Thermic effect of food is a component of total daily energy expenditure (TDEE). Some literature suggests lower postprandial rise in energy expenditure predicts future weight gain. It is also known that other components of TDEE, resting metabolic rate (RMR) and free-living physical activity energy expenditure, are prone to change in response to exercise training. However, most studies estimate thermic effect of food as a proportion of TDEE and thus have not evaluated whether changes in postprandial thermogenesis occur in response to exercise training. The objective of this study was to determine whether postprandial thermogenesis changed after completing aerobic exercise training in older women. Hypothesis: We hypothesize that the postprandial thermogenesis decreases in sedentary older women who complete 16-week aerobic exercise training. Methods: Sedentary older women (n = 47; age = 65.1 ± 4.3 years) completed 16-week moderate-intensity aerobic exercise training. RMR and 5-hour postprandial thermogenesis following ingesting the same meal, before and at the end of training, was measured via indirect calorimetry. The meal consisted of approximately 40% of each woman’s RMR at baseline. Postprandial thermogenesis was calculated as area under the curve. TDEE was also measured using doubly labelled water before and at the end of training. Results: After exercise training, RMR and TDEE did not change (p > 0.05 for both). Total postprandial thermogenesis (from 287 ±36 to 276 ± 40 kcal for 5 hours, p = 0.008) and postprandial thermogenesis in the first hour (from 69.9±8.7 to 66.3±8.1 kcal, p = 0.05) decreased significantly. The ratios of total and first-hour postprandial thermogenesis to TDEE also decreased (p = 0.026 and 0.013, respectively). Conclusion: Postprandial thermogenesis following the same meal reduced after aerobic training in older women. This adaptive change may contribute to an individual’s ability to defend the body’s energy store.

The relationship between “food addiction” and visceral adiposity in young females

ObjectivesThere is increasing interest in the role of addictive-like eating in weight gain. No studies have investigated associations between addictive-like eating and specific patterns of fat deposition which are sensitive indicators of chronic disease risk. This exploratory study aimed to evaluate relationships between Yale Food Addiction Scale (YFAS) assessed “food addiction” and visceral adiposity. MethodsAustralian adults aged 18–35years were recruited to an online survey including demographics and the YFAS. The YFAS is a 25-item tool designed to assess addictive-like eating behaviors and uses two scoring outputs, “diagnosis” and “symptom scores”. Participants had their anthropometric measurements taken [height, weight and body composition (visceral fat, fat mass, percentage body fat)] using a standardized protocol. ResultsNinety-three female participants (age 24.3±4.0years, BMI 24.3±6.0kg/m2) completed all measurements. Twenty-one participants (22.3%) met the predefined criteria for YFAS “diagnosis”. YFAS “symptom scores” were moderately correlated with visceral fat area (r=0.36, p<0.001), and “symptom scores” predicted increases in visceral fat area [r2=0.17, β=1.17, p=0.001]. Effect sizes were moderate for all variables. ConclusionThis study showed that YFAS assessed FA was associated with visceral fat deposition, a sensitive indicator of increased cardiometabolic risk. Future research is required to investigate whether FA predicts future weight gain.

Childhood cardiovascular risk factors, a predictor of late adolescent overweight.

Background:We conducted a prospective study to elucidate the effects of increased cardiovascular risk factors on future weight gain and also the relation between body mass index (BMI) and other cardiovascular risk factors in children and adolescents.Materials and Methods:This study was conducted on 1525 nonobese children and adolescents with an age range of 3-16 years old, participating in the 1st phase and follow-up phases of Tehran Lipid and Glucose Study. The subjects were evaluated 4 times with a 3-year time interval regarding lipid profile status and BMI, and other cardiovascular disease (CVD) risk factors. All the cases had a BMI <85% and had been appraised in at least two evaluation points.Results:Cardiovascular risk factors, high-density lipoprotein (HDL) (P = 0.019), low-density lipoprotein (P = 0.016), triglyceride (TG) (P < 0.001), and blood pressure (BP) (P = 0.001); had significant effects on weight gain. There was also no difference between boys and girls and no age trend for increasing weight in both groups. The associations between BMI with cardiovascular risk factors were assessed cross-sectionally. For both sexes, BMI was significantly correlated to systolic and diastolic BP and TG (P = 0.05). For girls, BMI was significantly related to HDL (P = 0.05) regardless to age, but in boys, the relation of BMI with HDL only increased with age (P = 0.05).Conclusion:Increased CVD risk factors are predictors of future overweight in childhood and adolescent and increased weight is linked significantly with dyslipidemia and hypertension in this age group.

Short-term variability in body weight predicts long-term weight gain

Body weight in lower animals and humans is highly stable despite a very large flux in energy intake and expenditure over time. Conversely, the existence of higher-than-average variability in weight may indicate a disruption in the mechanisms responsible for homeostatic weight regulation. In a sample chosen for weight-gain proneness, we evaluated whether weight variability over a 6-mo period predicted subsequent weight change from 6 to 24 mo. A total of 171 nonobese women were recruited to participate in this longitudinal study in which weight was measured 4 times over 24 mo. The initial 3 weights were used to calculate weight variability with the use of a root mean square error approach to assess fluctuations in weight independent of trajectory. Linear regression analysis was used to examine whether weight variability in the initial 6 mo predicted weight change 18 mo later. Greater weight variability significantly predicted amount of weight gained. This result was unchanged after control for baseline body mass index (BMI) and BMI change from baseline to 6 mo and for measures of disinhibition, restrained eating, and dieting. Elevated weight variability in young women may signal the degradation of body weight regulatory systems. In an obesogenic environment this may eventuate in accelerated weight gain, particularly in those with a genetic susceptibility toward overweight. Future research is needed to evaluate the reliability of weight variability as a predictor of future weight gain and the sources of its predictive effect. The trial on which this study is based is registered at clinicaltrials.gov as NCT00456131.

Weak Satiety Responsiveness Is a Reliable Trait Associated with Hedonic Risk Factors for Overeating among Women

Some individuals exhibit a weak satiety response to food and may be susceptible to overconsumption. The current study identified women showing consistently low or high satiety responses to standardised servings of food across four separate days and compared them on behavioural, psychological and physiological risk factors for overeating and future weight gain. In a crossover design, 30 female participants (age: 28.0 ± 10.6; body mass index (BMI): 23.1 ± 3.0) recorded sensations of hunger in the post-prandial period following four graded energy level breakfasts. Satiety quotients were calculated to compare individuals on satiety responsiveness across conditions. Body composition, resting metabolic rate (RMR), energy intake, food reward and craving, and eating behaviour traits were assessed under controlled laboratory conditions. A distinct low satiety phenotype (LSP) was identified with good consistency across separate study days. These individuals had a higher RMR, greater levels of disinhibition and reported feeling lower control over food cravings. Further, they consumed more energy and exhibited greater wanting for high-fat food. The inverse pattern of characteristics was observed in those exhibiting a consistently high satiety phenotype (HSP). Weak satiety responsiveness is a reliable trait identifiable using the satiety quotient. The LSP was characterised by distinct behavioural and psychological characteristics indicating a risk for overeating, compared to HSP.

Replacing sugary drinks with milk is inversely associated with weight gain among young obesity-predisposed children.

The aim of the present study was to examine the associations of sugary drink consumption and its substitution with alternative beverages with body weight gain among young children predisposed to future weight gain. Secondary analysis of the Healthy Start Study, a 1·5-year randomised controlled trial designed to prevent overweight among Danish children aged 2-6 years (n 366), was carried out. Multivariate linear regression models were used to investigate the associations of beverage consumption with change in body weight (Δweight) or BMI(ΔBMI) z-score. Substitution models were used to extrapolate the influence of replacing sugary drinks with alternative beverages (water, milk and diet drinks) on Δweight or ΔBMI z-score. Sugary drink intake at baseline and substitution of sugary drinks with milk were associated with both Δweight and ΔBMI z-score. Every 100 g/d increase in sugary drink intake was associated with 0·10 kg and 0·06 unit increases in body weight (P=0·048) and BMI z-score (P=0·04), respectively. Substitution of 100 g/d sugary drinks with 100 g/d milk was inversely associated with Δweight (β=-0·16 kg; P=0·045) and ΔBMI z-score (β=-0·07 units; P=0·04). The results of this study suggest that sugary drink consumption was associated with body weight gain among young children with high predisposition for future overweight. In line with the current recommendations, sugary drinks, whether high in added or natural sugar, should be discouraged to help prevent childhood obesity. Milk may be a good alternative to sugary drinks with regard to weight management among young obesity-predisposed children.

Abstract P239: Could Uric Acid Levels Predict Success In Chronic Weight Loss?

Background: Obese individuals have higher prevalence of hyperuricemia (hyperUA) and with weight loss (WL) improved hyperUA. We previously reported that serum uric acid levels (UA) associated plasma norepinephrine (NE) could predict future weight gain and BP elevation, and that WL program combining diet + exercise was most effective on UA, WL and BP reductions, although diet had stronger effects on UA and BP reduction compared to exercise. Objective: In this study, we examined whether lower UA levels would predict future success and maintenance of chronic WL compared to higher UA levels in a 2 yr WL regimen with diet and exercise. Methods: 154 overweight/obese men (BMI&gt;25 kg/m2) consisting of 89 normotensive and 65 untreated mild hypertensives were enrolled in the WL program with diet + exercise. The subjects had BP, BMI, Fat-mass, UA, plasma NE, insulin, glucose, HOMA-IR measured at entry, 6, 12, and 24 months. WL was defined as ≥10% WL. Results: 95 subjects succeeded significant WL at 24 month including 34 subjects in WL Maintenance group (WL was observed at both 6 and 24 m), and 61 subjects with Slow WL (WL was observed at only 24 m). At entry, serum UA and plasma NE in WL group (WL maintenance + Slow WL) were slightly lower compared to those in non-WL groups (WL&lt;10% at 24 m). Especially the slow WL group had significantly lower UA at entry compared to the non-WL group and WL maintenance group. Plasma UA and NE levels in the WL group were significantly lower than the non-WL group. Percent (%) reductions of UA and NE were greater in WL group than non-WL group. In all subjects, baseline UA and % changes of UA correlated with % changes in BMI over 24 m (R=0.205, P&lt;0.05; R=0.230, P&lt;0.05, respectively). Baseline UA correlated with % changes in UA, changes in Fat-mass, and changes in BMI (R=0.210, P&lt;0.05; R=0.197, P&lt;0.05; R=0.185, P&lt;0.05, respectively). Plasma NE at entry correlated with changes in UA and % changes in UA in all subjects (R=0.263, P&lt;0.05; R=0.412, P&lt;0.01). BP reductions at 24 m correlated with WL and baseline UA in all subjects (R=0.345, P&lt;0.05; R=0.247, P&lt;0.05) respectively). Conclusions: Serum UA and plasma NE levels may predict success in chronic WL with WL regimens, and may predict BP reduction associated with WL.

Helpful or harmful? Prospective association between weight misperception and weight gain among overweight and obese adolescents and young adults.

Weight misperception is common among adolescents with obesity, but it is not known whether weight perception is related to future weight gain. The objective of the study was to examine the prospective association between accurate weight perception versus weight misperception and weight change among youth who are overweight or obese. Using a subsample of The National Longitudinal Study of Adolescent to Adult Health Wave II cohort, we used linear regression modeling (adjusted for age, baseline body mass index (BMI), parental education, household percent federal poverty level, depression, race and ethnicity) to examine the prospective association between weight misperception (that is, perceiving oneself to be under or normal weight) among 2738 overweight and obese youth and subsequent BMI change from Wave II (1996) to Wave IV (2008-2009). Mean age at baseline (Wave II) was 15.9 (0.1). Fifty-seven percent of males and 80% of females accurately perceived themselves as overweight. In fully adjusted models, weight misperception was associated with less BMI gain among youth who were overweight and obese. Specifically, youth who perceived themselves to be at a healthy weight had lower BMI gains (males: β= -1.43, 95% confidence interval (CI)=(-2.26, -0.60), P=0.001; females: β= -1.35, 95% CI=(-2.59, -0.11), P=0.035) from Wave II to IV relative to those who accurately perceived themselves as overweight or obese. Contrary to commonly held assumptions, weight misperception among a non-clinical sample of youth who were overweight or obese predicted lower future weight gain. Efficacy of efforts to correct weight misperception should be rigorously examined to assess for both intended and unintended consequences.

Perceived weight status and risk of weight gain across life in US and UK adults.

Correctly identifying oneself as being overweight is presumed to be a prerequisite to successful weight management. The present research examined the effect that perceiving oneself as being 'overweight' has on risk of future weight gain in US and UK adults. Data from three longitudinal studies; US National Longitudinal Study of Adolescent Health (Add Health) 2001/2002-2008/2009, UK National Child Development Study (NCDS) 1981-2002/2004, and Midlife in the United States (MIDUS) 1995/1996-2004/2005, were used to examine the impact of perceiving oneself as being overweight on weight gain across adulthood in over 14 000 US and UK adults. Participants who perceived their weight status as being overweight were at an increased risk of subsequent weight gain. This effect was observed irrespective of weight status at baseline and whether weight status perceptions were accurate or inaccurate. In the MIDUS sample, perceiving oneself as being overweight was associated with overeating in response to stress and this mediated the relationship between perceived overweight and weight gain. Perceiving oneself as being 'overweight' is counter-intuitively associated with an increased risk of future weight gain among US and UK adults.

Reward Region Responsivity Predicts Future Weight Gain and Moderating Effects of the TaqIA Allele.

Because no large prospective study has investigated neural vulnerability factors that predict future weight gain we tested whether neural response to receipt and anticipated receipt of palatable food and monetary reward predicted body fat gain over 3-year follow-up in healthy-weight adolescent humans and whether the TaqIA polymorphism moderates these relations. Elevated reward activation in response to food cues predicted future body fat gain. Elevated reward response to food receipt predicted body fat gain for adolescents with a TaqIA A2/A2 allele and lower reward response predicted body fat gain for those with a TaqIA A1 allele. Results imply that too much or too little dopamine signaling and reward region responsivity increases risk for overeating.

The way to her heart? Response to romantic cues is dependent on hunger state and dieting history: An fMRI pilot study

Normal weight historical dieters (HDs) are prone to future weight gain, and show higher levels of brain activation in reward-related regions after having eaten than nondieters (NDs) in response to food stimuli (Ely, Childress, Jagannathan, & Lowe, 2014), a similar pattern to that seen in obesity. We hypothesized that HDs are differentially sensitive after eating to rewards in general, and thus extended prior findings by comparing the same groups' brain activation when viewing romantic pictures compared to neutral stimuli while being scanned in a blood oxygenation level-dependent (BOLD) fMRI paradigm in a fasted and fed state. Results show that 1) in fed relative to fasted conditions, both HDs and NDs were more responsive in areas related to reward and 2) in HDs, greater fed versus fasted activation extended to areas linked to perception and goal-directed behavior. HDs relative to NDs were more responsive to romantic cues in the superior frontal gyrus when fasted and the middle temporal gyrus when fed. This pattern of response is similar to HDs' activation when viewing highly palatable food cues, and is consistent with research showing overlapping brain-based responses to sex, drugs and food.

“At What Cost?”: Problematising the Achievement of ‘Health’ through Thinness – The Case of Bariatric Surgery

“At What Cost?”: Problematising the Achievement of ‘Health’ through Thinness – The Case of Bariatric Surgery

Spontaneous regional brain activity links restrained eating to later weight gain among young women

Theory and prospective studies have linked restrained eating (RE) to risk for future weight gain and the onset of obesity, but little is known about resting state neural activity that may underlie this association. To address this gap, resting fMRI was used to test the extent to which spontaneous neural activity in regions associated with inhibitory control and food reward account for potential relations between baseline RE levels and changes in body weight among dieters over a one-year interval. Spontaneous regional activity patterns corresponding to RE were assessed among 50 young women using regional homogeneity (ReHo) analysis, which measured temporal synchronization of spontaneous fluctuations within a food deprivation condition. Analyses indicated higher baseline RE scores predicted more weight gain at a one-year follow-up. Furthermore, food-deprived dieting women with high dietary restraint scores exhibited more spontaneous local activity in brain regions associated with the expectation and valuation for food reward [i.e., orbitofrontal cortex (OFC)/ventromedial prefrontal cortex (VMPFC)] and reduced spontaneous local activity in inhibitory control regions [i.e., bilateral dorsal-lateral prefrontal cortex (DLPFC)] at baseline. Notably, the association between baseline RE and follow-up weight gain was mediated by decreased local synchronization of the right DLPFC in particular and, to a lesser degree, increased local synchronization of the right VMPFC. In conjunction with previous research, these findings highlight possible neural mechanisms underlying the relation between RE and risk for weight gain.

Influence of SNP*SNP interaction on BMI in European American adolescents: findings from the National Longitudinal Study of Adolescent Health

Adolescent obesity is predictive of future weight gain, obesity and adult onset severe obesity (body mass index [BMI] ≥40 kg m(-2) ). Despite successful efforts to identify Single Nucleotide Polymorphisms (SNPs) influencing BMI, <5% of the 40-80% heritability of the phenotype has been explained. Identification of gene-gene (G-G) interactions between known variants can help explain this hidden heritability as well as identify potential biological mechanisms affecting weight gain during this critical developmental period. We have recently shown distinct genetic effects on BMI across the life course, and thus it is important to examine the evidence for epistasis in adolescence. In adolescent participants of European descent from wave II of the National Longitudinal Study of Adolescent Health (Add Health, n = 5072, ages 12-21, 52.5% female), we tested 34 established BMI-related SNPs for G-G interaction effects on BMI z-score. We used mixed-effects regression, assuming multiplicative interaction models adjusting for age, sex and geographic region, with random effects for family and school. For 28 G-G interactions that were nominally significant (P < 0.05), we attempted to replicate our results in an adolescent sample from the Childhood European American Cohort from Philadelphia. In the replication study, one interaction (PRKD1-FTO) was significant after correction for multiple testing. Our results are suggestive of epistatic effects on BMI during adolescence and point to potentially interactive effects between genes in biological pathways important in obesity.