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From monogenic to polygenic obesity: recent advances.
Eur Child Adolesc Psychiatry 2010; 19(3):297-310EC

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/m(2) 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.

Authors+Show Affiliations

Department of Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Virchowstrasse 174, Essen, Germany. anke.hinney@uni-due.deNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

20127379

Citation

Hinney, Anke, et al. "From Monogenic to Polygenic Obesity: Recent Advances." European Child & Adolescent Psychiatry, vol. 19, no. 3, 2010, pp. 297-310.
Hinney A, Vogel CI, Hebebrand J. From monogenic to polygenic obesity: recent advances. Eur Child Adolesc Psychiatry. 2010;19(3):297-310.
Hinney, A., Vogel, C. I., & Hebebrand, J. (2010). From monogenic to polygenic obesity: recent advances. European Child & Adolescent Psychiatry, 19(3), pp. 297-310. doi:10.1007/s00787-010-0096-6.
Hinney A, Vogel CI, Hebebrand J. From Monogenic to Polygenic Obesity: Recent Advances. Eur Child Adolesc Psychiatry. 2010;19(3):297-310. PubMed PMID: 20127379.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - From monogenic to polygenic obesity: recent advances. AU - Hinney,Anke, AU - Vogel,Carla I G, AU - Hebebrand,Johannes, Y1 - 2010/02/03/ PY - 2009/08/06/received PY - 2010/01/14/accepted PY - 2010/2/4/entrez PY - 2010/2/4/pubmed PY - 2010/6/15/medline SP - 297 EP - 310 JF - European child & adolescent psychiatry JO - Eur Child Adolesc Psychiatry VL - 19 IS - 3 N2 - 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/m(2) 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. SN - 1435-165X UR - https://www.unboundmedicine.com/medline/citation/20127379/From_monogenic_to_polygenic_obesity:_recent_advances_ L2 - https://dx.doi.org/10.1007/s00787-010-0096-6 DB - PRIME DP - Unbound Medicine ER -