Figure 4. Neuroanatomical location and transcriptional similarity of brain cell types enriching for BMI GWAS variants.

(a) Sagittal mouse brain view showing the 22 BMI GWAS-enriched cell types. The first two letters in each cell type label denote the developmental compartment (ME, mesencephalon; DE, diencephalon; TE, telencephalon), letters three to five denote the neurotransmitter type (INH, inhibitory; GLU, glutamatergic) and the numerical suffix represents an arbitrary number assigned to the given cell type. (b) Circular dendrogram showing the similarity of all Mouse Nervous System dataset cell type expression specificity (ES_μ) values. Dendrogram edges colored by taxonomy described in Zeisel et al., 2018. Expectedly, the cell types clustered according to their neuroanatomical origin. For clarity, only the labels of the 22 BMI GWAS enriched cell types are shown.

Figure 4—figure supplement 1. Conditional analysis of BMI GWAS-enriched mouse nervous system cell types conditional genetic prioritization analysis of BMI-prioritized cell types.

We used S-LDSC to re-estimate genetic prioritization p-values, conditioning on each BMI-prioritized cell type. Columns indicate the cell type conditioned on. The left column (‘baseline’) shows the unconditioned results (as shown in main text Figure 3a). Cell-types are colored by their brain region as shown in main text Figure 3a. NA values are colored in white (diagonal values) indicate cases were the prioritized and conditioned cell types are identical. Asterisks (*) mark p-values passing the Bonferroni significance threshold (P_S-LDSC <0.05/265 from main text Figure 3a). All conditional CELLECT results are available in Figure 4—source data 1.

Figure 4—figure supplement 2. Correlation of mouse nervous system BMI GWAS-enriched cell types correlogram of cell type ES_μ Pearson’s correlations.

Cell types are ordered by hierarchical clustered using Ward’s method. The plot was generated using the ‘corrplot’ R package.