Two weight gain prevention strategies, one targeting small changes to diet and physical activity and a second targeting large changes, significantly reduced weight gain in young adulthood. We examined Show more
Two weight gain prevention strategies, one targeting small changes to diet and physical activity and a second targeting large changes, significantly reduced weight gain in young adulthood. We examined whether weight gain prevention blunts genetic risk for body weight increase and/or high density lipoprotein cholesterol (HDL-C) lowering over two years. Participants were 524 male and female young adults (mean age = 28.2, SD = 4.3; mean BMI = 25.5, SD = 2.6). Obesity-related SNPs accounting for ≥ 0.04% of the variance were genotyped and combined into a genetic risk score. For HDL-C, SNPs within CETP, LIPC and FADS2 were genotyped. The obesity-related genetic risk score did not predict change in BMI independently or in interaction with treatment arm. However, consistent with the prior literature, each copy of the HDL-C risk, C, allele at CETP rs3764261 was associated with lower HDL-C at baseline. Moreover, significant interaction between SNP and treatment arm for change in HDL-C was observed (p = 0.02). In the control group, HDL-C change was dependent upon rs3764261 (p = 0.004) with C allele carriers showing a continued reduction in HDL-C. In contrast, within the two intervention groups, HDL-C increased on average with no differential effect of rs3764261 (p > 0.24). Notably, even among carriers of the CC genotype, small and large change arms were associated with increased HDL-C and the control arm a reduction (p = 0.013). The C allele at CETP rs3764261 is a strong risk factor for low HDL-C in young adulthood but weight gain prevention may mitigate this risk. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: clinicaltrials.gov Identifier: NCT01183689, https://clinicaltrials.gov/. Show less
Genome-wide association studies (GWAS) have identified consistent associations with obesity. However, the mechanisms remain unclear. The objective was to determine the association between obesity susc Show more
Genome-wide association studies (GWAS) have identified consistent associations with obesity. However, the mechanisms remain unclear. The objective was to determine the association between obesity susceptibility loci and dietary intake. The association of GWAS-identified obesity risk alleles (FTO, MC4R, SH2B1, BDNF, INSIG2, TNNI3K, NISCH-STAB1, MTIF3, MAP2K5, QPCTL/GIPR, and PPARG) with dietary intake, measured through food-frequency questionnaires, was investigated in 2075 participants from the Look AHEAD (Action for Health in Diabetes) clinical trial. We adjusted for age, sex, population stratification, and study site. Obesity risk alleles at FTO rs1421085 significantly predicted more eating episodes per day (P = 0.001)-an effect that persisted after adjustment for body weight (P = 0.004). Risk variants within BDNF were significantly associated with more servings from the dairy product and the meat, eggs, nuts, and beans food groups (P ≤ 0.004). The risk allele at SH2B1 rs4788099 was significantly associated with more servings of dairy products (P = 0.001), whereas the risk allele at TNNI3K rs1514176 was significantly associated with a lower percentage of energy from protein (P = 0.002). These findings suggest that obesity risk loci may affect the pattern and content of food consumption among overweight or obese individuals with type 2 diabetes. The Look AHEAD Genetic Ancillary Study was registered at clinicaltrials.gov as NCT01270763 and the Look AHEAD study as NCT00017953. Show less