Genetics of body weight and obesity

Complex phenotypes, such as those represented by anthropometric characters, exhibit quantitative variation in their expression, resulting from the combined contribution of multiple genes acting cumulatively to produce their physical manifestation. While environmental factors such as diet also make a significant contribution to the observed variation in these traits, it is the individual’s unique genetic background that determines the response to these environmental factors. Recent advances in molecular and statistical genetics have provided a variety of tools that allow us to elucidate the genetic architecture underlying such complex phenotypes as anthropometric traits. Three general approaches have been used to date in the search for genes underlying common, complex phenotypes. The first approach focuses on a priori selected candidate genes believed to have some plausible role in the trait of interest (for example, obesity) on the basis of their known or presumed biological function. This approach has had limited success in identifying genes involved in the development of disease at the population level. An alternative approach attempts to localise genes and requires no presumptions on the function of the gene, and is based on the detection of unique patterns of segregation among related individuals. Chief among this type of approach has been linkage analysis. Recent advances in the ability to evaluate linkage analysis data from large family pedigrees has shown great promise in identifying genomic regions associated with the development of complex phenotypes such as obesity, but the identification of the specific causal genetic variants has remained somewhat elusive. In addition to genome-wide linkage analyses, the last couple of years have also seen the widespread application of genome-wide association analyses. This approach differs from the linkage approach by its primary use of large samples of unrelated individuals. Recently, RNA-based technologies have also started to be very useful in the identification of genes differentially expressed in tissues of healthy and diseased individuals. This chapter reviews current knowledge of the genetic contribution to variation in anthropometric traits with a particular focus in those measures associated with obesity.