Genes, Obesity, and the Snowball Effect.
In The Secret Life of Fat, Sylvia Tara documented the effects of genetics on one’s propensity to gain weight and difficulty to lose it, all else being equal. (In fact, her personal experiences with these effects are what motivated Dr. Tara to investigate the genetics-fat link in the first place.)
“These genes,” Meyre told Science Daily, “may, in part, explain why some individuals experience uncontrolled and constant weight gain across their life, despite the availability of different therapeutic approaches.”
This is fascinating and important research that highlights the genetic pre-disposition to obesity and points at future models to detect genes and work towards individualized lifestyle programs to prevent obesity.
We caught up with Dr. Meyre to find out more.
ScienceToLiveBy: What specifically motivated this study into the genetics of obesity?
Dr David Meyre: While the average body mass index has reached a plateau in Western countries such as the United States, extreme forms of obesity are still on the rise. The origins of super obesity are still poorly understood (is it genes, environment, both?).
This is the reason why we studied the effects of 37 well-established obesity genes on body-mass index in 75,230 adults with European ancestry using innovative statistical methods (conditional quantile regression and meta-regression models).
We found that nine of the 37 genes (24%) make individuals gain more weight if they already have a high body mass index. The effect of these genes is amplified by four times, if we compare the 10% of the population at the low end of the body mass index, compared to the 10% at the high end. The plausible explanation is that there are interactions between these snowball obesity genes and risk environmental factors.
STLB: Explain the “snowball” effect? Is that a snowballing of the number of these nine genes that an individual has? Or having all nine means the higher your BMI gets, the faster it will continue to increase?
DR MEYRE: The number of bad copies (0, 1 or 2, one inherited from your father, one inherited from your mother) for each of these 9 genes is determined at conception. It can be comprised between 0 and 18 obesity risk copies depending on the individual.
Your second proposition is right. The bad copies at these genes make you gain weight, and when you get heavier, they make you gain even more weight (a vicious circle or snowball effect). The effect of these genes on weight gain can be four-times stronger if you compare the 10% lighter and 10% heavier people.
STLB: Are there certain individual or subsets of the nine genes identified that combine for part of the effect — or is it all nine that have to work together?
DR MEYRE: The nine genes do not interact with each other, so their effect is independent and sums up. The more obesity risk copies of the genes you inherit from your parents (from 0 to 18), the more you gain weight.
STLB: Is there an available way individuals can screen for these genes, these SNPs?
DR MEYRE: The effects of these nine genes is modest (it may contribute to 2% of body mass index variation in population) so genetic testing is not relevant for now. However, genetic testing of these snowball obesity genes may become relevant when we identify all of them (there are probably several hundred snowball genes disseminated on the whole genome). This may take couple of years.
STLB: What treatments, if any, do you see that could be developed based on knowing these all these genes and the snowball effect?
DR MEYRE: Prevention may be a more adequate option here. We already know that certain of these snowball obesity genes interact with lifestyle factors such as your diet, physical activity, sleeping habits, soda and alcohol drinking consumption habits.
The strategy in the long run may be to identify the subset of people who cumulate many of these snowball obesity early in life, and to propose a personalized lifestyle intervention program based on the genetic profile that minimizes the effect of these genes and maintains individuals in the low body mass index range.
STLB: What studies do you have planned to follow up on or compliment this study?
DR MEYRE: The next step is to generalize our discoveries in populations with non-European ancestry. More than 270 obesity genes have been recently identified in European, East Asian, South Asian, African, Native North American, South American and Pacific Islander populations, and more snowball obesity genes are likely to be found in the future.
We are also developing novel statistical and informatics methods to screen the entire human genome to track-down novel snowball obesity genes. Another important goal is to identify the specific lifestyles that interact with the snowball genes. The next steps are to improve the prediction, prevention and care of snowball obesity at the population level.