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. 2020 Sep 21;9:e55851. doi: 10.7554/eLife.55851

Figure 5. BMI GWAS enrichment across hypothalamic cells and human tissues.

(a) BMI GWAS enrichments across 347 hypothalamic cell types derived from studies of the Arc-ME (ARCME), the ventromedial hypothalamus (VMH), the lateral hypothalamus (LHA), the preoptic nucleus of the hypothalamus (POA) and the entire hypothalamus (HYPR and HYPC). For each study, CELLEX and CELLECT were run individually, and subsequently all cell types were pooled and significance was determine based on Bonferroni correction (p<0.05/347). Four cell types were significantly enriched, namely POA-NEURO66 (Reln+; Moffitt et al., 2018) and POA-NEURO21 (Cck+/Ebf3+; Moffitt et al., 2018) from the preoptic area of the hypothalamus, ARCME-NEURO29 (Sf1+/Adcyap1+; Campbell et al., 2017) from the Arc-ME, and LHA-NEURO20 (Ebf3/Otb+; Mickelsen et al., 2019) from the lateral hypothalamus. (b) CELLECT and high-confidence obesity genes enrichments for neuronal cell populations in the Arc-ME (upper panel). Expression of Mc4r, Pomc and Lepr across Arc-ME neuronal populations, white squares means that the given gene is not expressed in at least 10% of the cells in the given cell population, non-white squares denote increasingly specific gene expression (lower panel). (c) CELLECT enrichment analysis of Genotype-Tissue Expression Consortium (GTEx) RNA-seq data. Orange bars denote significantly enriched tissues. The hypothalamus datasets’ metadata, CELLECT results and expression specificity values for the enriched cell types are available in Figure 5—source datas 1–3. The GTEx tissue annotations, CELLECT and high-confidence obesity genes enrichment results are available in Figure 5—source datas 10–12. POA, preoptic area of the hypothalamus; LHA, lateral hypothalamus; ARCME, arcuate nucleus and median eminence complex; S-LDSC, stratified-linkage disequilibrium score regression.

Figure 5—source data 1. Hypothalamus datasets metadata.
Figure 5—source data 2. Hypothalamus CELLECT results.
elife-55851-fig5-data2.xlsx (214.6KB, xlsx)
Figure 5—source data 3. Hypothalamus expression specificity results.
elife-55851-fig5-data3.xlsx (748.9KB, xlsx)
Figure 5—source data 4. High-confidence obesity genes.
Figure 5—source data 5. High-confidence obesity genes expression specificities.
Figure 5—source data 6. High-confidence obesity genes enrichments.
Figure 5—source data 7. High-confidence obesity genes CELLECT correlations.
Figure 5—source data 8. Expression specificity and cell type heterogeneity.
Figure 5—source data 9. High-confidence obesity genes CELLEX top quartile.
Figure 5—source data 10. Genotype-Tissue Expression data annotation.
Figure 5—source data 11. Genotype-Tissue Expression CELLECT enrichment results.
Figure 5—source data 12. Genotype-Tissue Expression obesity genes enrichment results.

Figure 5.

Figure 5—figure supplement 1. Arc-ME neuronal cell population enrichments and expression levels across obesity genes CELLECT and high-confidence obesity genes enrichments for neuronal cell populations in the Arc-ME (upper panel).

Figure 5—figure supplement 1.

Expression of high-confidence obesity genes across Arc-ME neuronal populations, white squares means that the given gene is not expressed in at least 10% of the cells in the given cell population, non-white squares denote increasingly specific gene expression (lower panel).
Figure 5—figure supplement 2. Convergence of cell type prioritization based on common and rare variants.

Figure 5—figure supplement 2.

(a) Cell type prioritization of high-confidence obesity genes enrichment results (bar chart, left part) and BMI GWAS-enrichment results (bubble chart, right part). Circle sizes represent the -log10(Penrichment) cell type enrichment of the high-confidence obesity genes. Circles with black edges mark cell types passing the Bonferroni significance threshold (Penrichment <0.05/265). Bar chart (left plot) shows the distribution of -log10(Penrichment) across all cell types. Dashed lines indicate Bonferroni significance threshold. Cell types are grouped by the cell type taxonomy shown in Figure 3b. (b) Comparison of cell type BMI GWAS-enrichment and high-confidence obesity genes enrichment-based results. Cell type BMI GWAS-enrichment (x-axis) and cell type enrichment of high-confidence obesity genes (y-axis). Pearson’s correlation (R) is shown in the top left corner. Dashed lines indicate cell types passing the Bonferroni significance threshold. Solid line shows x = y relationship.
Figure 5—figure supplement 3. High-confidence obesity genes enrichment in mouse nervous system cell types.

Figure 5—figure supplement 3.

(a) Heatmap showing ESμ values for high-confidence obesity genes (columns) for BMI GWAS-enriched cell types (rows). (b) Cell type enrichment of high-confidence obesity genes for BMI GWAS-enriched cell types. The high-confidence obesity genes and mouse nervous system enrichment results are available in Figure 5—source datas 4 and 6.