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Polygenic obesity in humans.
Obes Facts 2008; 1(1):35-42OF

Abstract

The molecular genetic analysis of obesity has led to the identification of a limited number of confirmed major genes. While such major genes have a clear influence on the development of the phenotype, the underlying mutations are however (extremely) infrequent and thus of minor clinical importance only. The genetic predisposition to obesity must thus be polygenic; a number of such variants should be found in most obese subjects; however, these variants predisposing to obesity are also found in normal weight and even lean individuals. Therefore, a polygene can only be identified and validated by statistical analyses: the appropriate gene variant (allele) occurs more frequently in obese than in non-obese subjects. Each single polygene makes only a small contribution to the development of obesity. The 103Ile allele of the Val103Ile single nucleotide polymorphism (SNP) of the melanocortin-4 receptor gene (MC4R) was the first confirmed polygenetic variant with an influence on the body mass index (BMI); the more common Val103 allele is more frequent in obese individuals. As determined in a recent, large-scaled meta-analysis the effect size of this allele on mean BMI was approximately -0.5 kg/m(2). The first genome-wide association study (GWA) for obesity, based on approximately 100,000 SNPs analyzed in families of the Framingham study, revealed that a SNP in the proximity of the insulin-induced gene 2 (INSIG2) was associated with obesity. The positive result was replicated in independent samples; however, some other study groups detected no association. Currently, a meta-analysis is ongoing; its result will contribute to the evaluation of the importance of the INSIG2 polymorphism in body weight regulation. SNP alleles in intron 1 of the fat mass and obesity associated gene (FTO) confer the most relevant polygenic effect on obesity. In the first GWA for extreme early onset obesity we substantiated that variation in FTO strongly contributes to early onset obesity.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

20054160

Citation

Hinney, Anke, and Johannes Hebebrand. "Polygenic Obesity in Humans." Obesity Facts, vol. 1, no. 1, 2008, pp. 35-42.
Hinney A, Hebebrand J. Polygenic obesity in humans. Obes Facts. 2008;1(1):35-42.
Hinney, A., & Hebebrand, J. (2008). Polygenic obesity in humans. Obesity Facts, 1(1), pp. 35-42. doi:10.1159/000113935.
Hinney A, Hebebrand J. Polygenic Obesity in Humans. Obes Facts. 2008;1(1):35-42. PubMed PMID: 20054160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polygenic obesity in humans. AU - Hinney,Anke, AU - Hebebrand,Johannes, Y1 - 2008/02/08/ PY - 2010/1/8/entrez PY - 2008/1/1/pubmed PY - 2010/7/9/medline SP - 35 EP - 42 JF - Obesity facts JO - Obes Facts VL - 1 IS - 1 N2 - The molecular genetic analysis of obesity has led to the identification of a limited number of confirmed major genes. While such major genes have a clear influence on the development of the phenotype, the underlying mutations are however (extremely) infrequent and thus of minor clinical importance only. The genetic predisposition to obesity must thus be polygenic; a number of such variants should be found in most obese subjects; however, these variants predisposing to obesity are also found in normal weight and even lean individuals. Therefore, a polygene can only be identified and validated by statistical analyses: the appropriate gene variant (allele) occurs more frequently in obese than in non-obese subjects. Each single polygene makes only a small contribution to the development of obesity. The 103Ile allele of the Val103Ile single nucleotide polymorphism (SNP) of the melanocortin-4 receptor gene (MC4R) was the first confirmed polygenetic variant with an influence on the body mass index (BMI); the more common Val103 allele is more frequent in obese individuals. As determined in a recent, large-scaled meta-analysis the effect size of this allele on mean BMI was approximately -0.5 kg/m(2). The first genome-wide association study (GWA) for obesity, based on approximately 100,000 SNPs analyzed in families of the Framingham study, revealed that a SNP in the proximity of the insulin-induced gene 2 (INSIG2) was associated with obesity. The positive result was replicated in independent samples; however, some other study groups detected no association. Currently, a meta-analysis is ongoing; its result will contribute to the evaluation of the importance of the INSIG2 polymorphism in body weight regulation. SNP alleles in intron 1 of the fat mass and obesity associated gene (FTO) confer the most relevant polygenic effect on obesity. In the first GWA for extreme early onset obesity we substantiated that variation in FTO strongly contributes to early onset obesity. SN - 1662-4025 UR - https://www.unboundmedicine.com/medline/citation/20054160/Polygenic_obesity_in_humans_ L2 - https://www.karger.com?DOI=10.1159/000113935 DB - PRIME DP - Unbound Medicine ER -