The Genetic Determinants of Common Obesity-Susceptibility



Despite a relatively high heritability, the search for obesity-susceptibility genes has been challenging. While over the past 15 years, candidate gene studies and genome-wide linkage studies were able to identify only a handful of genetic variants convincingly associated with obesity-related traits, the genome-wide association approach has truly revolutionised gene discovery for many common diseases and traits, including obesity. In less than 4 years time, large-scale genome-wide association studies for body mass index, waist-to-hip ratio and extreme obesity have identified at least 50 obesity-susceptibility loci, most of which had not previously been linked to body weight regulation. Although the combined contribution of these genetic loci to the variation in obesity risk at the population level is small and their predictive value is low, it is anticipated that the recently identified loci will shed new light on the complex physiology that governs the regulation of energy balance and fat distribution. The expectation is that the genetic loci will point towards novel causal pathways and, subsequently, to the identification of therapeutic targets within these pathways. This new knowledge could eventually lead to the development of agents for more effective preventive and therapeutic interventions. While the rapid progress in gene discovery has raised hopes towards the development of genetic risk profiles to guide individual weight management, the current evidence suggests that the available genetic data is not sufficient for such personalised implementations.


Obesity Genetic epidemiology Heritability Candidate gene study Genome-wide linkage study Genome-wide association study Translation Genetic prediction 


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.MRC Epidemiology UnitInstitute of Metabolic ScienceCambridgeUK

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