Genetics of Severe Obesity

PURPOSE OF REVIEW: This review aims to present current information on genes underlying severe obesity, with the main emphasis on the three genes LEP, LEPR and MC4R. RECENT FINDINGS: There is a substantial amount of evidence that variants in at least ten different genes are the cause of severe monogenic obesity. The majority of these are involved in the leptin-melanocortin signalling pathway. Due to the frequency of some of the identified variants, it is clear that monogenic variants also make a significant contribution to common obesity. SUMMARY: The artificial distinction between rare monogenic obesity and common polygenic obesity is now obsolete with the identification of MC4R variants of strong effect in the general population.