Fig. 5: Neuronal clusters are enriched for genes linked to BMI variation in the general population.

a, Prioritization of 452 human hypothalamic cell types (C4) identified 291 cell types as significantly enriched for associations in the BMI GWAS. Cell types were grouped by cluster level C1 (neurons) and C0 (non-neurons). Dashed line represents the Bonferroni significance threshold, P < 0.00011 (two-tailed). Clusters are coloured based on their assigned regions, as seen in Fig. 3. Extended data are shown in Supplementary Table 17. b–g, Variant-level associations in identified effector genes in UK Biobank. Rare exome variant associations with BMI for variants within BSN (b), CALCR (c), CORO1A (d), MC4R (e), PCSK1 (f) and POMC (g). Variant collapsing masks included variants with a MAF < 0.1% and annotated as either high-confidence PTV (HC_PTV) or HC_PTV plus missense variants with a high CADD score (greater than or equal to 25, denoted DMG). Each variant association is represented by a circle and vertical line: line length, P value (−log₁₀), in the direction of its effect on BMI in carriers of the rare allele; circle size, number of carriers of each variant (allele count). Exons are indicated by boxes and connected by the intron line. Extended data, including individual P values, are shown in Supplementary Tables 18 and 19.