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Recent Progress in the Understanding of Obesity: Contributions of Genome-Wide Association Studies

Overview
Journal Curr Obes Rep
Specialty Endocrinology
Date 2015 Sep 17
PMID 26374640
Citations 9
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Abstract

Since 2007, discovery of genetic variants associated with general obesity and fat distribution has advanced tremendously through genome-wide association studies (GWAS). Currently, the number of robustly associated loci is 190. Even though these loci explain <3 % of the variance, they have provided us a still emerging picture of genomic localization, frequency and effect size spectra, and hints of functional implications. The translation into biological knowledge has turned out to be an immense task. However, in silico enrichment analyses of genes involved in specific pathways or expressed in specific tissues have the power to suggest biological mechanisms underlying obesity. Inspired by this, we highlight genes in five loci potentially mechanistically linked to leptin-receptor trafficking and signaling in primary cilia. The clinical application of genetic knowledge as prediction, prevention, or treatment strategies is unfortunately still far from reality. Thus, despite major advances, further research is warranted to solve one of the greatest health problems in modern society.

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References
1.
Monda K, Chen G, Taylor K, Palmer C, Edwards T, Lange L . A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat Genet. 2013; 45(6):690-6. PMC: 3694490. DOI: 10.1038/ng.2608. View

2.
Bluher M . Adipokines - removing road blocks to obesity and diabetes therapy. Mol Metab. 2014; 3(3):230-40. PMC: 3986498. DOI: 10.1016/j.molmet.2014.01.005. View

3.
Snijder M, Dekker J, Visser M, Bouter L, Stehouwer C, Kostense P . Associations of hip and thigh circumferences independent of waist circumference with the incidence of type 2 diabetes: the Hoorn Study. Am J Clin Nutr. 2003; 77(5):1192-7. DOI: 10.1093/ajcn/77.5.1192. View

4.
Wen W, Zheng W, Okada Y, Takeuchi F, Tabara Y, Hwang J . Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index. Hum Mol Genet. 2014; 23(20):5492-504. PMC: 4168820. DOI: 10.1093/hmg/ddu248. View

5.
Wang Z, Li V, Chan G, Phan T, Nudelman A, Xia Z . Adult type 3 adenylyl cyclase-deficient mice are obese. PLoS One. 2009; 4(9):e6979. PMC: 2735775. DOI: 10.1371/journal.pone.0006979. View