Despite the prevalence of obesity – every third US adult is obese – its pathogenesis remains largely unknown. Obesity, defined as body mass index (BMI) >30, is caused by a sustained positive energy balance and an incremental resetting of the body weight set point. From studies of extreme obesity in humans and rodent studies, it is known that energy homeostasis in part is regulated by hypothalamic melanocortin signaling, however, mutations in genes encoding these brain circuits only account for a modest number of obesity cases. Integration of results from genome-wide association studies (GWAS) for BMI with relevant gene expression data has proven to be an agnostic and powerful approach to identify known and novel biological cell types underlying a range of traits and disease. Drawing on recent GWAS for BMI from >700,000 individuals and murine single cell transcriptomics data covering >500,000 cells throughout >300 cell types across the mouse nervous system, we have developed an approach to identify novel cell types and cell type-specific biological pathways likely etiologic to obesity. During the talk, I will discuss conceptual and methodological issues, present preliminary results and relate these to findings from the hypothalamic melanocortin system.