Genetic Basis

Abstract

Knowledge on the genetic basis of obesity has undergone significant development in recent years as a result of optimization, greater speed and reduction in the costs of omics technologies. However, despite this development, many question marks still remain on which genes are the most important in increasing obesity risk and what the contribution of environmental factors is in increasing or decreasing genetic susceptibility. Research into the environmental factors that may promote or neutralize genetic susceptibility to obesity is also increasing in complexity, given that every day more potential contributors are revealed. Hence, we have moved on from investigating the main classic environmental factors (the environmental factor being understood as all that which is not genetic), mainly focusing on diet physical activity, to now consider a wider range of environmental factors, outstanding among which are socio-economic status, educational level, drug consumption, stress, tobacco, sleep habits, meal times or microbiota, among others. Obesity, therefore, even though it may have a strong genetic basis in some individuals, is, for the majority of the population, the result of the interaction between genetic and environmental factors, and so greater genetic susceptibility to obesity can be modulated by environmental factors and vice versa. Despite several initial studies on twins providing percentages of environmental and genetic contributions to obesity (e.g., 40% genetic and 60% environmental), it must be said that these estimates in percentages vary considerably and change a great deal depending on the population analyzed and the methodology employed. For that reason, it is now accepted that, apart from in very few cases of monogenic obesity in which a very strong genetic component exists alongside strong heredity, under most circumstances the obesity phenotype is the result of the interaction between the genetic and the environmental contribution in a balance that appears to vary over time. This introduces a dynamic factor to the genetics of obesity which is not fully understood yet and is still being investigated. It is known that several genetic variants have a greater influence on obesity phenotypes in the early stages of life, whereas others seem to have a greater influence in later life. Nevertheless, more longitudinal studies are required that include individuals from birth to old age in order study the variability of the genetic contribution more accurately from a more dynamic point of view, as well as to study the main interactions with environmental factors during different stages of life. Apart from age, gender may also be another of the factors that have an additional influence on contributing to genetic susceptibility. The additional modulations of gene–environment interactions depending on gender have not been widely studied, so a greater number of studies are required. Recently there has been more interest shown in investigating the genetic and environmental contribution to obesity from a gender perspective, which will provide important data in the not too distant future. Likewise, the possible differences between ethnic groups for some of the genetic variants related with obesity and their environmental modulation need to be researched in greater detail. It is clear from all this that, quite apart from the great genetic heterogeneity that exists in obesity, there are also other factors such as age, gender and ethnicity that together with multiple environmental factors may be capable of modulating genetic susceptibility, so giving rise to a wide range of phenotypes and interactions related with obesity, and that these are different in each individual. Understanding these individual characteristics in detail is essential in the new framework of so-called Precision Medicine. In this article we shall review the most recent knowledge on the genetic bases of obesity, also taking into account that these genetic variants cannot be studied in isolation, but have to be integrated into the study of environmental factors.