there has to be a physical effect that causes the imbalance. The effects of a gene (or disease) can be measured directly by measuring food intake, digestion waste products, and the energy output
Yes, there are physiological items that effect the burning efficiencies, the desires, the conversion of material into fat and other items. However, the bottom line is that weight gain will not occur unless there is more calories taken in than are released into the environment. Likewise there cannot be weight loss unless somehow more calories are released into the environment than taken in. If you do not believe it try to go without any calories taken in for a few years and see if you do not loose weight.
Of course the question is why do some take in more, or use (or expel) less.