The value of genetic variation in the prediction of obesity

Abstract

Obesity is predominantly caused by an unhealthy lifestyle, but genetic factors also contribute to people’s susceptibility to gain weight. Rare high-risk mutations have been identified that cause extreme and early-onset obesity in a fraction of the population, while numerous common low-risk loci have been identified through genome-wide association studies that contribute to obesity in the general population. As insights into the contribution of genetic variation to obesity increase, the interest in using genetic variants to predict who is at risk to gain weight has also increased. Before constructing risk models, however, one needs to have a clear view on what form of obesity needs to be predicted, why, in whom, and for what purpose. Obesity is multifactorial, in that it results from an interplay between genes and environmental risk factors, such that models solely based on genetic variants will be unlikely to reach high predictive ability, as we illustrate using the literature on currently identified BMI-associated loci. Furthermore, it seems that irrespective of the poor predictive ability, communicating genetic information does not seem effective in making people adopt a healthy lifestyle. While using genetic information in the prediction of obesity is a legitimate aim, we believe that the most valuable contribution of gene discovery studies lies in their contribution to elucidate new physiological pathways that underlie obesity susceptibility, which in turn could lead to the identification of therapeutic targets and make its way into mainstream health care.