Genotype effect of the MC4R rs7227255 on trajectory of changes in craving in the high-protein (A) and the low-protein (B) diet groups over 24 mo in overweight and obese adults. Linear mixed models were used to test genetic associations with the trajectory of changes in appetite-related measures according to diet groups. Time was treated as a repeated measurement factor, and genotype × time interaction terms were included in the mixed models. Values are means ± SEs. P values were adjusted for age, sex, ethnicity, baseline BMI, and baseline values for craving. Data included 408, 324, and 235 overweight and obese adults in the low-protein (15% of energy) diet group and 403, 332, and 259 overweight and obese adults in the high-protein (25% of energy) diet group for craving at baseline and at 6 and 24 mo, respectively. The question “How strong is your desire to eat? (‘0 = very weak’ to ‘100 = very strong’)” was used to assess craving. MC4R, melanocortin-4 receptor.