Relation of the multilocus genetic composite reflecting high dopamine signaling capacity to future increases in BMI

Because food intake exerts its rewarding effect by increasing dopamine (DA) signaling in reward circuitry, it theoretically follows that individuals with a greater number of genotypes putatively associated with high DA signaling capacity are at increased risk for overeating and subsequent weight gain. We tested the association between the multilocus genetic composite risk score, defined by the total number of genotypes putatively associated with greater DA signaling capacity (i.e. TaqIA A2 allele, DRD2-141C Ins/Del and Del/Del genotypes, DRD4-S allele, DAT1-S allele, and COMT Val/Val genotype), and future increases in Body Mass Index (BMI) in three prospective studies. Participants in Study 1 (N = 30; M age = 15.2; M baseline BMI = 26.9), Study 2 (N = 34; M age = 20.9; M baseline BMI = 28.2), and Study 3 (N = 162; M age = 15.3, M baseline BMI = 20.8) provided saliva samples from which epithelial cells were collected, permitting DNA extraction. The multilocus genetic composite risk score was associated with future increases in BMI in all three studies (Study 1, r = 0.37; Study 2, r = 0.22; Study 3, r = 0.14) and the overall sample (r = 0.19). DRD4-S was associated with increases in BMI in Study 1 (r = 0.42), Study 2 (r = 0.27), and in the overall sample (r = 0.17). DAT1-S was associated with increases in BMI in Study 3 (r = 0.17) and in the overall sample (r = 0.12). There were no associations between the other genotypes (TaqIA, COMT, and DRD2-141C) and change in BMI over 2-year follow-up. Data suggest that individuals with a genetic propensity for greater DA signaling capacity are at risk for future weight gain and that combining alleles that theoretically have a similar function may provide a more reliable method of modeling genetic risk associated with future weight gain than individual genotypes.