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

• 146 genetic variants are associated with BMI or WHRadjBMI in the GIANT consortium.
• The vast majority of GWAS identified variants lie in non-coding areas of the genome.
• In silico methods begins to unravel the biology underlying the genetic associations.
• Specific mechanisms in synaptic signaling and neurotransmitter release are pinpointed.

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.