pathways of interest: adrenergic (ADR2A, ADRB3); fat mass (FTO), receptor-cellular function (GNB3), serotonergic (5-HTTLPR),GLP-1 pathway (TCF7L2), thermogenesis (UCP-2, UCP3), bile acids (GPBAR1) loci. Methods: 271 overweight or obese, predominantly Caucasian, participants underwent, on separate days, validated measurements of intermediate phenotypes: GE of solids and liquids by scintigraphy, gastric volume (GV) by SPECT during fasting and after 200mL Ensure® (Δ GV), satiety by kcal intake (T-kcal) during a buffet meal 4h after the Ensure® meal, satiation (maximal tolerated volume, MTV) by Ensure® ingested at 30mL/min, and fasting and postprandial GLP-1 (by radioimmunoassay). We genotyped, with TaqMan® SNP Assay, 16 variants in the genes of ADR2A, ADRB3, UCP-2, UCP-3, FTO, 5-HTTLPR, TCF7L2, GNB3, and GPBAR1 [minor allele frequencies (MAF) in table]. We assessed the association of each genotype with each intermediate phenotype using an ANCOVA (adjusting for age and gender). Results: 271 participants (188 females, 83 males), mean age 36.7±1.2y, BMI 32.9±0.3kg/m2. The table shows significant univariate associations of gene SNPs with the intermediate phenotypes (bolded for those with p<0.05). The main findings are summarized by mechanism or pathway: adrenergic, ADRA2C (rs2234888) with GE of liquids; fat mass, FTO (rs9939609) with GE of solids and liquids; GLP-1 pathway, TCF7L2 (rs7903146) with GE of solids; thermogenesis UCP3 (rs2075577) with satiation, (rs15763) with satiety, and (rs1626521) with GE of liquids, Δ GV, satiation and satiety; and bile acids, GPBAR1 (rs11554825) with satiation. Conclusion: Genes associated with T2DM or obesity also alter certain gastric motor functions, satiation or satiety. Variants in UCPs are associated with all three domains of energy intake investigated, that is, gastric motor function, satiation and satiety. The FTO (A) allele is associated with accelerated GE for solids and liquids, suggesting a pathophysiological mechanism for its association with development of obesity. The UCP data suggest that mitochondrial proteins alter gastric motor function in addition to known effects on energy metabolism, and both may impact food intake. Support: NIH DK67071 Univariate associations of obesity candidate genes with intermediate phenotypes