To identify specific genes that may account for BMI association, we considered each of the following to represent supportive evidence for a gene within a locus: (1) the gene nearest the index SNP26; (2) genes containing missense, nonsense or copy number variants, or a cis-expression quantitative trait locus (eQTL) in LD with the index SNP; (3) genes prioritized by integrative methods implemented in DEPICT; (4) genes prioritized by connections in published abstracts by GRAIL (Gene Relationships Across Implicated Loci)27; or (5) genes biologically related to obesity, related metabolic disease, or energy expenditure based on manual literature review (Tables 1 and 2, Extended Data Tables 2–4 and Supplementary Tables 23–25). We first focused on the 64 genes in associated loci with more than one consistent line of supporting evidence. As expected, many of these genes overlap with CNS processes, including synaptic function, cell–cell adhesion, and glutamate signalling (ELAVL4, GRID1, CADM2, NRXN3, NEGR1 and SCG3), cause monogenic obesity syndromes (MC4R, BDNF, BBS4 and POMC), or function in extreme/early onset obesity in humans and mouse models (SH2B1 and NEGR1)6,28,29. Other genes with several
