Exposure to positive peer sentiment about nicotine replacement therapy in an online smoking cessation community is associated with NRT use.

BACKGROUND: Little is known about the influence of online peer interactions on health behavior change. This study examined the relationship between exposure to peer sentiment about nicotine replacement therapy (NRT) in an online social network for smoking cessation and NRT use. METHODS: Participants were 3297 current smokers who enrolled in an Internet smoking cessation program, participated in a randomized trial, and completed a 3-month follow-up. Half received free NRT as part of the trial. Automated text classification identified 27,038 posts about NRT that one or more participants were exposed to in the social network. Sentiment towards NRT was rated on Amazon Mechanical Turk. Participants' exposure to peer sentiment about NRT was determined by analysis of clickstream data. Modified Poisson regression examined self-reported use of NRT at 3-months as a function of exposure to NRT sentiment, controlling for study arm and post exposure. RESULTS: One in five participants (19.3%, n = 639) were exposed to any NRT-related posts (mean exposure = 6.5 ±â€¯14.7, mean sentiment = 5.4 ±â€¯0.8). The association between sentiment exposure and NRT use varied by receipt of free NRT. Greater exposure to positive NRT sentiment was associated with an increased likelihood of NRT use among participants who did not receive free NRT (adjusted rate ratio 1.22, 95% CI 1.01, 1.47; p = .043), whereas no such relationship was observed among participants who did receive free NRT (p = .48). CONCLUSIONS: Exposure to positive sentiment about NRT was associated with increased NRT use when smokers obtained it on their own. Highlighting user-generated content containing positive NRT sentiment may increase NRT use among treatment-seeking smokers.

Improving Adherence to Smoking Cessation Treatment: Smoking Outcomes in a Web-based Randomized Trial.

Background: Partial adherence in Internet smoking cessation interventions presents treatment and evaluation challenges. Increasing adherence may improve outcomes. Purpose: To present smoking outcomes from an Internet randomized trial of two strategies to encourage adherence to tobacco dependence treatment components: (i) a social network (SN) strategy to integrate smokers into an online community and (ii) free nicotine replacement therapy (NRT). In addition to intent-to-treat analyses, we used novel statistical methods to distinguish the impact of treatment assignment from treatment utilization. Methods: A total of 5,290 current smokers on a cessation website (WEB) were randomized to WEB, WEB + SN, WEB + NRT, or WEB + SN + NRT. The main outcome was 30-day point prevalence abstinence at 3 and 9 months post-randomization. Adherence measures included self-reported medication use (meds), and website metrics of skills training (sk) and community use (comm). Inverse Probability of Retention Weighting and Inverse Probability of Treatment Weighting jointly addressed dropout and treatment selection. Propensity weights were used to calculate Average Treatment effects on the Treated. Results: Treatment assignment analyses showed no effects on abstinence for either adherence strategy. Abstinence rates were 25.7%-32.2% among participants that used all three treatment components (sk+comm +meds).Treatment utilization analyses revealed that among such participants, sk+comm+meds yielded large percentage point increases in 3-month abstinence rates over sk alone across arms: WEB = 20.6 (95% CI = 10.8, 30.4), WEB + SN = 19.2 (95% CI = 11.1, 27.3), WEB + NRT = 13.1 (95% CI = 4.1, 22.0), and WEB + SN + NRT = 20.0 (95% CI = 12.2, 27.7). Conclusions: Novel propensity weighting approaches can serve as a model for establishing efficacy of Internet interventions and yield important insights about mechanisms. Clinical Trials.gov: NCT01544153.

A prospective examination of online social network dynamics and smoking cessation.

INTRODUCTION: Use of online social networks for smoking cessation has been associated with abstinence. Little is known about the mechanisms through which the formation of social ties in an online network may influence smoking behavior. Using dynamic social network analysis, we investigated how temporal changes of an individual's number of social network ties are prospectively related to abstinence in an online social network for cessation. In a network where quitting is normative and is the focus of communications among members, we predicted that an increasing number of ties would be positively associated with abstinence. METHOD: Participants were N = 2,657 adult smokers recruited to a randomized cessation treatment trial following enrollment on BecomeAnEX.org, a longstanding Internet cessation program with a large and mature online social network. At 3-months post-randomization, 30-day point prevalence abstinence was assessed and website engagement metrics were extracted. The social network was constructed with clickstream data to capture the flow of information among members. Two network centrality metrics were calculated at weekly intervals over 3 months: 1) in-degree, defined as the number of members whose posts a participant read; and 2) out-degree-aware, defined as the number of members who read a participant's post and commented, which was subsequently viewed by the participant. Three groups of users were identified based on social network engagement patterns: non-users (N = 1,362), passive users (N = 812), and active users (N = 483). Logistic regression modeled 3-month abstinence by group as a function of baseline variables, website utilization, and network centrality metrics. RESULTS: Abstinence rates varied by group (non-users = 7.7%, passive users = 10.7%, active users = 20.7%). Significant baseline predictors of abstinence were age, nicotine dependence, confidence to quit, and smoking temptations in social situations among passive users (ps < .05); age and confidence to quit among active users. Among centrality metrics, positive associations with abstinence were observed for in-degree increases from Week 2 to Week 12 among passive and active users, and for out-degree-aware increases from Week 2 to Week 12 among active users (ps < .05). CONCLUSIONS: This study is the first to demonstrate that increased tie formation among members of an online social network for smoking cessation is prospectively associated with abstinence. It also highlights the value of using individuals' activities in online social networks to predict their offline health behaviors.

Prenatal environmental chemical exposures and longitudinal patterns of child neurobehavior.

BACKGROUND: Prenatal chemical exposures may adversely affect neurodevelopment, but few studies have examined the persistence of these associations. We examined whether associations between prenatal bisphenol A (BPA) or polybrominated diphenyl ether (PBDE) exposures persist or resolve as children age. METHODS: We followed 346 mother-child pairs (enrolled 2003-2006) from Cincinnati, OH from pregnancy until children were 8 years old. We measured BPA in urine collected at 16 and 26 weeks gestation and PBDE-47 in serum collected at 16 weeks gestation. We administered repeated measures of children's behavior, mental/psychomotor development, and IQ from ages 1-8 years. We determined if associations of BPA or PBDE-47 with child neurobehavior persisted or resolved as children aged using linear mixed models and estimated neurobehavioral measure reproducibility using intraclass correlation coefficients (ICCs). RESULTS: Higher BPA in girls and higher PBDE-47 in both boys and girls were associated with more externalizing behaviors; these associations persisted from ages 2-8 years (exposure×age interaction p-values≥0.36). Higher PBDE-47 concentrations were associated with decreases in MDI from ages 1-3 years (PBDE-47x age interaction p-value=0.03) and persistently lower IQ at ages 5 and 8 years (PBDE-47×age interaction p-value=0.56). Mental/psychomotor abilities had fair reproducibility from ages 1-3 years (ICCs∼0.4), cognitive abilities from ages 5 to 8 years had excellent reproducibility (ICCs=0.7-0.8), and parent-reported behaviors from ages 2-8 years had poor to good reproducibility (ICCs=0.38-0.59). CONCLUSIONS: Prenatal BPA and PBDE-47 concentrations were persistently associated with more externalizing behaviors. PBDE-47 concentrations were inversely associated with cognitive abilities that strengthened over time.

Improving Adherence to Smoking Cessation Treatment: Intervention Effects in a Web-Based Randomized Trial.

BACKGROUND: Web-based smoking cessation interventions can deliver evidence-based treatments to a wide swath of the population, but effectiveness is often limited by insufficient adherence to proven treatment components. This study evaluated the impact of a social network (SN) intervention and free nicotine replacement therapy (NRT) on adherence to evidence-based components of smoking cessation treatment in the context of a Web-based intervention. METHODS: A sample of adult U.S. smokers (N = 5290) was recruited via BecomeAnEX.org, a free smoking cessation Web site. Smokers were randomized to one of four arms: (1) an interactive, evidence-based smoking cessation Web site (WEB) alone; (2) WEB in conjunction with an SN intervention designed to integrate participants into the online community (WEB+SN); (3) WEB plus free NRT (WEB+NRT); and (4) the combination of all treatments (WEB+SN+NRT). Adherence outcomes assessed at 3-month follow-up were as follows: Web site utilization metrics, use of skills training components, intratreatment social support, and pharmacotherapy use. RESULTS: WEB+SN+NRT outperformed all others on Web site utilization metrics, use of practical counseling tools, intratreatment social support, and NRT use. It was the only intervention to promote the sending of private messages and the viewing of community pages over WEB alone. Both social network arms outperformed WEB on most metrics of online community engagement. Both NRT arms showed higher medication use compared to WEB alone. CONCLUSIONS: This study demonstrated the effectiveness of two approaches for improving adherence to evidence-based components of smoking cessation treatment. Integrated approaches to medication provision and social network engagement can enhance adherence to components known to improve cessation. IMPLICATIONS: This study demonstrated that an integrated approach to medication provision and social network integration, when delivered through an online program, can enhance adherence across all three recommended components of an evidence-based smoking cessation program (skills training, social support, and pharmacotherapy use). Nicotine replacement therapy-when provided as part of an integrated program-increases adherence to other program elements, which in turn augment its own therapeutic effects. An explicit focus on approaches to improve treatment adherence is an important first step to identifying leverage points for optimizing intervention effectiveness.

FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials.

OBJECTIVE:  To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN:  Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURCES:  Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015. ELIGIBILITY CRITERIA FOR STUDY SELECTION:  Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity. RESULTS:  We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category. CONCLUSIONS:  We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions. SYSTEMATIC REVIEW REGISTRATION:  PROSPERO CRD42015015969.

Baseline Characteristics and Generalizability of Participants in an Internet Smoking Cessation Randomized Trial.

BACKGROUND: The potential for sampling bias in Internet smoking cessation studies is widely recognized. However, few studies have explicitly addressed the issue of sample representativeness in the context of an Internet smoking cessation treatment trial. PURPOSE: The purpose of the present study is to examine the generalizability of participants enrolled in a randomized controlled trial of an Internet smoking cessation intervention using weighted data from the National Health Interview Survey (NHIS). METHODS: A total of 5290 new users on a smoking cessation website enrolled in the trial between March 2012 and January 2015. Descriptive statistics summarized baseline characteristics of screened and enrolled participants, and multivariate analysis examined predictors of enrollment. Generalizability analyses compared demographic and smoking characteristics of trial participants to current smokers in the 2012-2014 waves of NHIS (n = 19,043) and to an NHIS subgroup based on Internet use and cessation behavior (n = 3664). Effect sizes were obtained to evaluate the magnitude of differences across variables. RESULTS: Predictors of study enrollment were age, gender, race, education, and motivation to quit. Compared to NHIS smokers, trial participants were more likely to be female, college educated, and daily smokers and to have made a quit attempt in the past year (all effect sizes 0.25-0.60). In comparisons with the NHIS subgroup, differences in gender and education were attenuated, while differences in daily smoking and smoking rate were amplified. CONCLUSIONS: Few differences emerged between Internet trial participants and nationally representative samples of smokers, and all were in expected directions. This study highlights the importance of assessing generalizability in a focused and specific manner. CLINICALTRIALS.GOV: #NCT01544153.

Online community use predicts abstinence in combined Internet/phone intervention for smoking cessation.

OBJECTIVE: To estimate the causal effects of online community use on 30-day point prevalence abstinence at 3 months among smokers that received a combined Internet/phone intervention for smoking cessation. METHOD: Participants were 399 adult smokers selected from the combined Internet/phone arm of The iQUITT Study (Graham et al., 2011), a randomized trial of Internet and proactive telephone counseling for smoking cessation. All selected participants had accessed a web-based smoking-cessation program with an established online community and received at least one telephone counseling call. Automated tracking metrics of passive (e.g., reading posts, viewing profiles) and active (e.g., writing posts, sending messages) community use were extracted at 3 months. Self-selected community use defined the groups of interest as None, Passive, and Both (passive and active). Inverse probability of treatment weighting corrected for baseline imbalances on demographic, smoking, and psychosocial variables. Propensity weights estimated via generalized boosted models were used to calculate average treatment effects (ATE) and average treatment effects on the treated (ATT). RESULTS: Patterns of community use were None = 145 (36.3%), Passive = 82 (20.6%), and Both = 172 (43.1%). ATE-weighted abstinence rates were None = 12.2% (95% CI = 6.7-17.7), Passive = 25.2% (95% CI = 15.1-35.2), and Both = 35.5% (95% CI = 28.1-42.9). ATT-weighted abstinence rates indicated even greater benefits of passive community use by nonusers. CONCLUSIONS: More than 1/3 of the participants who used the community both passively and actively achieved abstinence. Participation in an established online community as part of a combined Internet/phone intervention has the potential to promote short-term abstinence. Results also demonstrated that information and support that originate in the community can serve as a resource for all users. (PsycINFO Database Record

Lifestyle Intervention for Weight Loss and Cardiometabolic Changes in the Setting of Glucokinase Regulatory Protein Inhibition: Glucokinase Regulatory Protein-Leu446Pro Variant in Look AHEAD.

BACKGROUND: Glucokinase regulatory protein (GCKR) inhibitors offer a novel treatment approach for glucose control in diabetes mellitus; however, their cardiometabolic effects, particularly in relation to increased triglycerides and C-reactive protein (CRP) levels, are of concern. GCKR Leu446Pro is a common variant associated with reduced GCKR function, increased triglycerides, and CRP. METHODS AND RESULTS: We investigated whether a 1-year intensive lifestyle intervention (ILI) for weight loss would avert the unfavorable cardiometabolic effects associated with GCKR Leu446Pro when compared with a diabetes mellitus support and education arm in overweight/obese individuals with type 2 diabetes mellitus with triglyceride (n=3214) and CRP (n=1411) data participating in a randomized lifestyle intervention study for weight loss, Action for Health in Diabetes Mellitus (Look AHEAD). Once demographics, medication use and baseline adiposity, and fitness were accounted for, ILI did not modify the baseline association of GCKR-Leu446Pro with elevated triglycerides (ß±SE=0.067±0.013, P=1.5×10(-7) and ß±SE=0.052±0.015, P=5×10(-4)) or with elevated CRP (ß±SE=0.136±0.034, P=5.1×10(-5)and ß±SE=0.903±0.038, P=0.015) in the overall sample and Non-Hispanic Whites, respectively. The lack of a protective effect from ILI at 1 year when compared with diabetes mellitus support and education (ILI versus diabetes mellitus support and education interaction for triglyceride and CRP change, respectively: P=0.64 and 0.37 in the overall sample; P=0.27 and 0.05 in Non-Hispanic Whites) persisted after additional adjustment for changes in adiposity and fitness. CONCLUSIONS: Moderate improvements in adiposity and fitness with ILI did not mitigate the adverse cardiometabolic effects of GCKR inhibition in overweight/obese individuals with diabetes mellitus.

Use of an online smoking cessation community promotes abstinence: Results of propensity score weighting.

OBJECTIVE: We estimated the causal effects of use of an online smoking cessation community on 30-day point prevalence abstinence at 3 months. METHODS: Participants (N = 492) were adult current smokers in the enhanced Internet arm of The iQUITT Study, a randomized trial of Internet and telephone treatment for smoking cessation. All participants accessed a Web-based smoking-cessation program that included a large, established online community. Automated tracking metrics of passive (e.g., reading forum posts, viewing member profiles) and active (e.g., writing forum posts, sending private messages) community use were extracted from the site at 3 months. Self-selected community use defines the groups of interest: "None," "Passive," and "Both" (passive + active). Inverse probability of treatment weighting corrected for baseline imbalances on demographic, smoking, psychosocial, and medical history variables. Propensity weights estimated via generalized boosted models were used to calculate Average Treatment Effects (ATE) and Average Treatment effects on the Treated (ATT). RESULTS: Patterns of community use were: None = 198 (40.2%), Passive = 110 (22.4%), and Both = 184 (37.4%). ATE-weighted abstinence rates were: None = 4.2% (95% CI = 1.5-6.9); Passive = 15.1% (95% CI = 8.4-21.9); Both = 20.4% (95% CI = 13.9-26.8). ATT-weighted abstinence rates indicated even greater benefits of community use. CONCLUSIONS: Community users were more likely to quit smoking at 3 months than nonusers. The estimated benefit from use of online community resources was even larger among subjects with high propensity to use them. No differences in abstinence emerged between passive and passive/active users. Results suggest that lurking in online communities confers specific abstinence benefits. Implications of these findings for online cessation communities are discussed.

Genetic Predictors of Depressive Symptoms in the Look AHEAD Trial.

OBJECTIVES: Numerous studies have found elevated depressive symptoms among individuals with Type 2 diabetes, yet the mechanisms remain unclear. We examined whether genetic loci previously associated with depressive symptoms predict depressive symptoms among overweight/obese individuals with Type 2 diabetes or change in depressive symptoms during behavioral weight loss. METHODS: The Illumina CARe iSelect (IBC) chip and Cardiometabochip were characterized in 2118 overweight or obese participants with Type 2 diabetes from Look AHEAD (Action for Health in Diabetes), a randomized trial to determine the effects of intensive life-style intervention and diabetes support and education on cardiovascular morbidity and mortality. Primary analyses focused on baseline Beck Depression Inventory (BDI) scores and depressive symptom change at 1 year. RESULTS: Of eight single nucleotide polymorphisms (SNPs) in six loci, three a priori SNPs in two loci (chromosome 5: rs60271; LBR: rs2230419, rs1011319) were associated with baseline BDI scores, but in the opposite direction of prior research. In joint analysis of 90,003 IBC and Cardiometabochip SNPs, rs1543654 in the region of KCNE1 predicted change in BDI scores at Year 1 in diabetes support and education (ß = -1.05, standard error [SE] = 0.21, p = 6.9 × 10(-7)) at the level of chip-wide significance, while also showing a nominal association with baseline BDI (ß = 0.35, SE = 0.16, p = .026). Adjustment for antidepressant medication and/or limiting analyses to non-Hispanic white individuals did not meaningfully alter results. CONCLUSIONS: Previously reported genetic associations with depressive symptoms did not replicate in this cohort of overweight/obese individuals with Type 2 diabetes. We identified KCNE1 as a potential novel locus associated with depressive symptoms.

Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials.

Clinically relevant weight loss is achievable through lifestyle modification, but unintentional weight regain is common. We investigated whether recently discovered genetic variants affect weight loss and/or weight regain during behavioral intervention. Participants at high-risk of type 2 diabetes (Diabetes Prevention Program [DPP]; N = 917/907 intervention/comparison) or with type 2 diabetes (Look AHEAD [Action for Health in Diabetes]; N = 2,014/1,892 intervention/comparison) were from two parallel arm (lifestyle vs. comparison) randomized controlled trials. The associations of 91 established obesity-predisposing loci with weight loss across 4 years and with weight regain across years 2-4 after a minimum of 3% weight loss were tested. Each copy of the minor G allele of MTIF3 rs1885988 was consistently associated with greater weight loss following lifestyle intervention over 4 years across the DPP and Look AHEAD. No such effect was observed across comparison arms, leading to a nominally significant single nucleotide polymorphism×treatment interaction (P = 4.3 × 10(-3)). However, this effect was not significant at a study-wise significance level (Bonferroni threshold P < 5.8 × 10(-4)). Most obesity-predisposing gene variants were not associated with weight loss or regain within the DPP and Look AHEAD trials, directly or via interactions with lifestyle.

A common variant in the CLDN7/ELP5 locus predicts adiponectin change with lifestyle intervention and improved fitness in obese individuals with diabetes.

Overweight/obese individuals with Type 2 diabetes have low adiponectin levels, which may improve with lifestyle changes. We investigated whether genetic variants associated with adiponectin levels in genome-wide association studies (GWAS) would also be related with adiponectin changes in response to an intensive lifestyle intervention (ILI), potentially through mechanisms altering the adipose microenvironment via weight loss and/or improved cardiorespiratory fitness. Look AHEAD was a randomized trial comparing the cardiovascular benefits of ILI-induced weight loss and physical activity compared with diabetes support and education among overweight/obese individuals with Type 2 diabetes. In a subsample of Look AHEAD with adiponectin data and genetic consent (n=1,351), we evaluated the effects of 24 genetic variants, demonstrated by GWAS to be cross-sectionally associated with adiponectin, on adiponectin change 1-yr postintervention. We explored via mediational analyses whether any differential effects by treatment arm were occurring through weight loss and/or improved fitness. A variant, rs222857, in the CLDN7 locus, potentially associated with epithelial barrier integrity and tight junction physiology, and a putative cis expression quantitative trail locus for elongator acetyltransferase complex subunit 5 (ELP5), predicted adiponectin increases within ILI (log-adiponectin in overall sample per copy: ß±SE=0.05±0.02, P=0.008; in non-Hispanic whites: 0.06±0.02, P=0.009). The favorable effects of rs222857 (minor allele frequency 45.5%) appeared to be mediated by mechanisms associated with improved fitness, and not weight loss. This is the first study to identify a genetic variant that modifies adiponectin response to lifestyle intervention in overweight/obese diabetic individuals.

Genetic modifiers of cardiorespiratory fitness response to lifestyle intervention.

PURPOSE: Numerous prospective studies indicate that improved cardiorespiratory fitness reduces type 2 diabetes risk and delays disease progression. We hypothesized that genetic variants modify fitness response to an intensive lifestyle intervention (ILI) in the Action for Health in Diabetes (Look AHEAD) randomized clinical trial, aimed to detect whether ILI will reduce cardiovascular events in overweight/obese subjects with type 2 diabetes compared with a standard of care. METHODS: Polymorphisms in established fitness genes and in all loci assayed on the Illumina CARe iSelect chip were examined as predictors of change in MET level, estimated using a treadmill test, in response to a 1-yr intervention in 3899 participants. RESULTS: We identified a significant signal in previously reported fitness-related gene RUNX1 that was associated with 1-yr METs response in ILI (0.19 ± 0.04 MET less improvement per minor allele copy; P = 1.9 × 10(-5)) and genotype-intervention interaction (P = 4.8 × 10(-3)). In the chipwide analysis, FKBP7 rs17225700 showed a significant association with ILI response among subjects not receiving beta-blocker medications (0.47 ± 0.09 METs less improvement; P = 5.3 × 10(-5)) and genotype-treatment interaction (P = 5.3 × 10(-7)). The Gene Relationships Among Implicated Loci pathway-based analysis identified connections between associated genes, including those influencing vascular tone, muscle contraction, cardiac energy substrate dynamics, and muscle protein synthesis. CONCLUSIONS: This is the first study to identify genetic variants associated with fitness responses to a randomized lifestyle intervention in overweight/obese diabetic individuals. RUNX1 and FKBP7, involved in erythropoesis and muscle protein synthesis, respectively, are related to change in cardiorespiratory fitness in response to exercise.

Human cardiovascular disease IBC chip-wide association with weight loss and weight regain in the look AHEAD trial.

BACKGROUND/AIMS: The present study identified genetic predictors of weight change during behavioral weight loss treatment. METHODS: Participants were 3,899 overweight/obese individuals with type 2 diabetes from Look AHEAD, a randomized controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education, on cardiovascular outcomes. Analyses focused on associations of single nucleotide polymorphisms (SNPs) on the Illumina CARe iSelect (IBC) chip (minor allele frequency >5%; n = 31,959) with weight change at year 1 and year 4, and weight regain at year 4, among individuals who lost ≥ 3% at year 1. RESULTS: Two novel regions of significant chip-wide association with year-1 weight loss in ILI were identified (p < 2.96E-06). ABCB11 rs484066 was associated with 1.16 kg higher weight per minor allele at year 1, whereas TNFRSF11A, or RANK, rs17069904 was associated with 1.70 kg lower weight per allele at year 1. CONCLUSIONS: This study, the largest to date on genetic predictors of weight loss and regain, indicates that SNPs within ABCB11, related to bile salt transfer, and TNFRSF11A, implicated in adipose tissue physiology, predict the magnitude of weight loss during behavioral intervention. These results provide new insights into potential biological mechanisms and may ultimately inform weight loss treatment.

Do genetic modifiers of high-density lipoprotein cholesterol and triglyceride levels also modify their response to a lifestyle intervention in the setting of obesity and type-2 diabetes mellitus?: The Action for Health in Diabetes (Look AHEAD) study.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) and triglycerides are cardiovascular risk factors susceptible to lifestyle behavior modification and genetics. We hypothesized that genetic variants identified by genome-wide association studies as associated with HDL-C or triglyceride levels modify 1-year treatment response to an intensive lifestyle intervention, relative to a usual care of diabetes mellitus support and education. METHODS AND RESULTS: We evaluated 82 single-nucleotide polymorphisms, which represent 31 loci demonstrated by genome-wide association studies to be associated with HDL-C and triglycerides, in 3561 participants who consented for genetic studies and met eligibility criteria. Variants associated with higher baseline HDL-C levels, cholesterol ester transfer protein (CETP) rs3764261 and hepatic lipase (LIPC) rs8034802, were found to be associated with HDL-C increases with intensive lifestyle intervention (P=0.0038 and 0.013, respectively) and had nominally significant treatment interactions (P=0.047 and 0.046, respectively). The fatty acid desaturase-2 rs1535 variant, associated with low baseline HDL-C (P=0.017), was associated with HDL-C increases with intensive lifestyle intervention (0.0037) and had a nominal treatment interaction (P=0.035). Apolipoprotein B (rs693) and LIPC (rs8034802) single-nucleotide polymorphisms showed nominally significant associations with HDL-C and triglyceride changes with intensive lifestyle intervention and a treatment interaction (P<0.05). Phosphatidylglycerophosphate synthase-1 single-nucleotide polymorphisms (rs4082919) showed the most significant triglyceride treatment interaction in the full cohort (P=0.0009). CONCLUSIONS: This is the first study to identify genetic variants modifying lipid responses to a randomized lifestyle behavior intervention in overweight or obese individuals with diabetes mellitus. The effects of genetic factors on lipid changes may differ from the effects on baseline lipids and are modifiable by behavioral intervention.