Variations in specific genes contribute to individual differences in quantitative traits such as weight, height, eye color, etc. These traits are influenced by several genes at the same time, so a single normal variant in one gene usually has only moderate influence overall. Since the differences are so small, mapping genetic variants in normal subjects requires a large amount of DNA samples. Clearly, when a single mutation causes severe impairments in function, it is possible to find the damaged gene in a small sample of the population. Thanks to the vast amount of subjects which were tested in the recent study, the researchers were able to find the common variants of a specific gene that influences body weight.
The study included 77,000 adult participants and involved collaboration between 77 institutions from the UK, USA, France, Germany, Italy, Finland, and Sweden. The researchers found that several variants close to the MC4R Gene cause weight gain. These results come in addition to a previously described FTO Gene, which also contributes to weight gain. Although the MC4R and FTO variants are in different areas in the genome, their influence on weight is additive, and it is possible that they influence similar functions. People that have both the FTO and MC4R variants are, in average, 3.8 kg (8.5 lb) heavier.
The MC4R protein is very important in bodily functions, as it influences many aspects of our physiology, including appetite regulation and energy expenditure. Previous research groups have shown that great impairments or total inactivation of the MC4R protein cause severe genetic obesity. Impairments in MC4R are the number one genetic cause of obesity worldwide.
In a further research project, which was conducted on a group of 6,000 children, the scientists found that the effect was almost twice as big as that seen in adults. Between ages four and seven, children with the described variants gained weight due to gain of fat tissue and not muscle tissue or any other solid tissues. It was found that children with the rarer MC4R mutations yield a more disrupted protein and have an even greater gain of fat as opposed to muscle and other tissue. This serves as proof that the common variants described above do indeed disrupt the activity of MC4R.
The next step of the research group will be to try and understand how the different genetic variants affect the activity of the MC4R Gene. The variants described in the study at hand are further away from MC4R in the genome. It is likely that these variants disrupt DNA areas that are required for normal activity or production of MC4R.
TFOT previously published a story describing a gene that prevents men from learning from their mistakes, which was found by scientists at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany. Another recent TFOT story concerns a gene modification on yeast, performed at the University of Southern California, which causes the yeast to achieve a ten fold life span.
More information on the MC4R research project can be found here.