Genetics of body composition: From severe obesity to extreme leanness
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Date
2020
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Abstract
This chapter describes common genetic variations influencing body composition as well as rare mutations causing monogenic obesity or extreme leanness. Large population-based genome-wide association studies (GWAS) revealed more than 500 genetic loci associated with body mass index (BMI) and adiposity traits in the population. Common variations in FTO and MC4R genes are the most statistically consistent signals across studies. Although discoveries of new gene variants through GWAS are important for expanding underlying knowledge on body fat accumulation, their small effect make them insufficient for predicting obesity. Most cases of monogenic obesity are derived from rare mutations in genes belonging to the leptin-melanocortin pathway, such as LEP, LEPR, MC4R, or POMC genes. On the other extreme of BMI, the study of congenital generalized lipodystrophy syndrome has revealed mutations in AGPAT2, BSCL2, PTRF, and CAV1 genes. The evaluation of obesity and leanness as opposite phenotypes represents an interesting approach to assessing causal gene variations related to body composition.
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Keywords
Genetic, Hyperphagia, Leanness, Leptin, Lipodystrophy, Melanocortin, Obesity