Genome-wide association studies of human adiposity: Zooming in on synapses

Abstract

The decade anniversary for genome-wide association studies (GWAS) is approaching, and this experimental approach has commenced a deeper understanding of the genetics underlying complex diseases. In obesity genetics the GIANT (Genetic Investigation of ANthropometric Traits) consortium has played a crucial role, recently with two comprehensive meta-analyses, one focusing on general obesity, analyzing body-mass index (BMI) and the other on fat distribution, focusing on waist-hip ratio adjusted for BMI. With the in silico methods applied in these two studies as the pivot, this review looks into some of the biological knowledge, beginning to emerge from the intricate genomic background behind the genetic determinants of human adiposity. These include synaptic dysfunction, where GWAS pinpoint potential new mechanisms in pathways already known to be linked with obesity.

Keywords: BMI; Fat distribution; Functional translation; GWAS; Genome-wide association study; Obesity.