Physical activity can reduce genetic risk to obesity

23 September 2010

In 2005, according to the World Health Organisation, around 1.6 billion adults and a further 20 million children under the age of five were overweight across the world. By 2015, there are expected to be more than 700 million obese adults (increasing from 400 million in 2005). Although this epidemic has largely been driven by changes in lifestyle, such as the increase in availability of calorie-rich foods coupled with an increasingly sedentary lifestyle, recent genome-wide association studies (GWAS) have shown that genetic factors also play an important role. A study published in PLoS Medicine assesses how a physically active lifestyle impacts on an individual’s genetic predisposition to obesity [Li et al. (2010) PLoS Med 7(8):e1000332. doi:10.1371/journal.pmed.1000332].

Using a large population-based study design, Li et al. genotyped 12 SNPs in obesity susceptibility loci in 20,000 individuals of white European descent. These SNPs were then used to calculate a genetic predisposition score based on adding the number of BMI-increasing alleles across the 12 SNPs. Physical activity was assessed by means of a validated self-administered questionnaire, with data available for 20,000 individuals at baseline and 12,000 at a second health check 3-4 years later. Interactions between the genetic predisposition scores and levels of physical activity were then assessed based on obesity risk and changes in BMI over time.

Li et al. found adding each BMI-increasing allele to an individual’s genetic predisposition score resulted in an increase in BMI equivalent to 445 grams body weight in an adult 1.70 metres tall. Increasing physical activity resulted in a decrease in BMI equivalent to 904g in body weight. Individuals with a physically active lifestyle have a smaller increase in body weight per increase in genetic predisposition (379g) whereas those with a physically inactive lifestyle exhibit a more pronounced increase in body weight (592g). Obesity risk per increase in genetic risk was also reduced in the physically active compared to the physically inactive.
 
Comment: Overweight and obesity are associated with serious health consequences. Increasing physically activity reduces obesity risk, and this advice was thought to be equally applicable to everyone. However, this large study shows that those individuals with a greater genetic predisposition to obesity may find this advice even more beneficial, prompting the question whether increased genetic risk can be effectively used in order to target interventions to a group that would have a greater gain.
 
A limitation of the study which the authors themselves acknowledge is that the participants self-reported their levels of activity. It would be both more difficult and more expensive to use a more objective measure of physical activity.

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