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Published in: European Child & Adolescent Psychiatry 3/2010

Open Access 01-03-2010 | Review

From monogenic to polygenic obesity: recent advances

Authors: Anke Hinney, Carla I. G. Vogel, Johannes Hebebrand

Published in: European Child & Adolescent Psychiatry | Issue 3/2010

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Abstract

The heritability of obesity and body weight in general is high. A small number of confirmed monogenic forms of obesity—the respective mutations are sufficient by themselves to cause the condition in food abundant societies—have been identified by molecular genetic studies. The elucidation of these genes, mostly based on animal and family studies, has led to the identification of important pathways to the disorder and thus to a deeper understanding of the regulation of body weight. The identification of inborn deficiency of the mostly adipocyte-derived satiety hormone leptin in extremely obese children from consanguineous families paved the way to the first pharmacological therapy for obesity based on a molecular genetic finding. The genetic predisposition to obesity for most individuals, however, has a polygenic basis. A polygenic variant by itself has a small effect on the phenotype; only in combination with other predisposing variants does a sizeable phenotypic effect arise. Common variants in the first intron of the ‘fat mass and obesity associated’ gene (FTO) result in an elevated body mass index (BMI) equivalent to approximately +0.4 kg/m² per risk allele. The FTO variants were originally detected in a genome wide association study (GWAS) pertaining to type 2 diabetes mellitus. Large meta-analyses of GWAS have subsequently identified additional polygenic variants. Up to December 2009, polygenic variants have been confirmed in a total of 17 independent genomic regions. Further study of genetic effects on human body weight regulation should detect variants that will explain a larger proportion of the heritability. The development of new strategies for diagnosis, treatment and prevention of obesity can be anticipated.
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Metadata
Title
From monogenic to polygenic obesity: recent advances
Authors
Anke Hinney
Carla I. G. Vogel
Johannes Hebebrand
Publication date
01-03-2010
Publisher
Springer-Verlag
Published in
European Child & Adolescent Psychiatry / Issue 3/2010
Print ISSN: 1018-8827
Electronic ISSN: 1435-165X
DOI
https://doi.org/10.1007/s00787-010-0096-6

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