Role of Genes in Obesity and Body Fat Distribution

By analyzing genetic samples from 224 459 individuals, researchers identified 49 genomic loci associated with waist-to-hip ratio (WHR), 33 of which are novel (Shungin D et al. Nature. 2015;518[7538]:187-196). Of these 49 loci, 19 showed significant sex-specific differences, suggesting that genetic regulation of fat distribution is sexually dimorphic. These genes influence body fat distribution by affecting fat cell development, blood vessel formation, transcriptional regulation, and insulin resistance.

A companion study conducted in 339 224 individuals identified 97 genomic loci associated with individuals’ body mass index (BMI) that have significant effects on various aspects of metabolism (Locke AE et al. Nature. 2015;518[7538]:197-206). Of these 97 BMI-associated loci, 56 are novel. The uncovered loci account for approximately 2.7% of BMI variation, and genome-wide estimates suggest that common variation overall accounts for as much as 21% of BMI variation.

The central nervous system appears to play a substantial role in BMI, and in contrast to WHR, BMI-associated genes include those involved in synaptic function, glutamate signaling, insulin secretion/action, energy metabolism, lipid biology, and adipogenesis. Furthermore, BMI-associated genes were not found to be sexually dimorphic.

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