PLOS Genetics: Emerging Function of Fat Mass and Obesity-Associated Protein (Fto)

Genome-wide association studies (GWAS) are a laborious but powerful tool to identify genetic risk factors associated with complex polygenic traits such as obesity [1], diabetes [2], or coronary artery disease [3]. The link between genetic variation in FTO and obesity was first described in a GWAS for type 2 diabetes [1] and was later independently confirmed in different populations all over the world. First described in 2007, genetic variation in FTO has since become one of the most solidly confirmed risk factor for polygenic obesity in humans; yet, information about how FTO affects metabolism is still scarce. Bioinformatic analyses suggestFTO codes for a Fe(II)- and 2-oxoglutarate–dependent nucleic acid demethylase [4][5] that catalyzes demethylation of 3-methylthymine in single-stranded DNA [5]. However, how this proposed function of FTO is integrated into the complex network of energy metabolism control remains the object of intense scientific investigation.

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