Second, we used DEPICT, that uses predefined gene sets reconstituted using coexpression data, to perform gene set enrichment analysis. After merging highly correlated gene sets, nearly 500 gene sets were significantly enriched (FDR < 0.05) for genes in BMI-associated loci (Fig. 2b and Supplementary Table 21a, b). The most strongly enriched gene sets highlight potentially novel pathways in the CNS. These include gene sets related to synaptic function, long-term potentiation and neurotransmitter signalling (glutamate signalling in particular, but also noradrenaline, dopamine and serotonin release cycles, and GABA (γ-aminobutyric acid) receptor activity; Fig. 2c). Potentially relevant mouse behavioural phenotypes, such as physical activity and impaired coordination were also highly enriched (Fig. 2b and Supplementary Table 21a). Several gene sets previously linked to obesity, such as integration of energy metabolism, polyphagia, secretion and action of insulin and related hormones (for example, ‘regulation of insulin secretion by glucagon-like peptide 1′ and ‘glucagon signalling in metabolic regulation’), mTOR signalling (which affects cell growth in response to nutrient intake via insulin and growth factors25), and gene sets overlapping the neurotrophin signalling pathway identified by MAGENTA
