Recent progress in the genetics of common obesity

Abstract

The genetic contribution to interindividual variation in common obesity has been estimated at 40–70%. Yet, despite a relatively high heritability, the search for obesity susceptibility genes has been an arduous task. This paper reviews recent progress made in the obesity genetics field with an emphasis on established obesity susceptibility loci identified through candidate gene as well as genome‐wide studies. For the last 15 years, candidate gene and genome‐wide linkage studies have been the two main genetic epidemiological approaches to identify genetic loci for common traits, yet progress has been slow and success limited. Only recently have candidate gene studies started to succeed; by means of large‐scale studies and meta‐analyses at least five variants in four candidate genes have been found to be robustly associated with obesity‐related traits. Genome‐wide linkage studies, however, have so far not been able to pinpoint genetic loci for common obesity. The genome‐wide association approach, which has become available in recent years, has dramatically changed the pace of gene discoveries for common disease, including obesity. Three waves of large‐scale high‐density genome‐wide association studies have already discovered at least 15 previously unanticipated genetic loci incontrovertibly associated with body mass index and extreme obesity risk. Although the combined contribution of these loci to the variation in obesity risk at the population level is small and their predictive value is typically low, these recently discovered loci are set to improve fundamentally our insights into the pathophysiology of obesity.

Linking genes with exercise: where is the cut-off?

“…Thus, we suggest that future studies using a genomic paradigm to expose molecular regulation should employ a more mechanistic approach and focus on functions that are more directly related to the molecular alteration under investigation. This call for a careful test of functional relevance for gene-phenotype associations is in line with suggestions voiced regarding the molecular mechanism of metabolic disease (Loos 2009). We suggest that future studies of whether or how a single gene polymorphism may affect _ VO 2 max or sprint performance in different populations will most likely not advance our understanding of the underlying mechanisms that determine performance during physical exercise.…”

Maternal obesity disturbs the postnatal development of gonocytes in the rat without impairment of testis structure at prepubertal age

“…A review concerning the genetics of obesity, with an emphasis on established obesity susceptibility loci identified through candidate gene and genome-wide studies, indicated that the contribution of genetic loci to body weight increase is !2% (Loos 2009). Therefore, environmental factors, such as high saturated fat in diets, are thought to have pivotal roles in overweight and obesity (Cascio et al 2012).…”

Association of the C825T polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a Taiwanese population

“…The social and economic costs of obesity are high as obesity elevates the risk of several medical complications, such as type 2 diabetes (T2D), hypertension, dyslipidemia, and cardiovascular disease (Kelly et al 2008;Ogden et al 2007). More and more genetic variants associated with obesity are being discovered using candidate gene approaches, genome-wide linkage studies, and genome-wide association studies (Hebebrand et al 2010;Loos 2009). Identification of genes that contribute to risk of obesity will allow identifying individuals who are at risk, and ultimately it may lead to new therapies for treatment and prevention (Hebebrand et al 2010;Loos 2009).…”

“…More and more genetic variants associated with obesity are being discovered using candidate gene approaches, genome-wide linkage studies, and genome-wide association studies (Hebebrand et al 2010;Loos 2009). Identification of genes that contribute to risk of obesity will allow identifying individuals who are at risk, and ultimately it may lead to new therapies for treatment and prevention (Hebebrand et al 2010;Loos 2009). The search for genes that increase the susceptibility to develop obesity has become increasingly important.…”