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MAGMA HBA

MAGMA was used to test the Johnston 20191 GWAS of Multisite Chronic Pain (MCP) using scRNAseq data from the Human Brain Atlas2 as a reference.

Results

The results are plotted below:

hba-magma-mcp

The x-axis corresponds to HBA cluster number, while the y-axis corresponds to the \(-\log_{10}(p)\) score produced by MAGMA. Clusters are colored according to their HBA supercluster. The dotted line denotes the Bonferroni significance threshold.

The most significant cell types are in the Caudate ganglionic eminences (CGE) interneuron supercluster.

After applying a stepwise selection algorithm similar to the one describe in Watanabe et al.3, three clusters were identified as independently significant:

Retained_clusters P Supercluster Class auto-annotation Neurotransmitter auto-annotation Neuropeptide auto-annotation Subtype auto-annotation Transferred MTG Label Top three regions Top Enriched Genes
Cluster286 1.8883e-07 CGE interneuron NEUR GABA CBLN CCK CHGA CHGB CORT CRH IGF NAMPT NPW NPY NUCB NXPH PNOC SCG SST UBL VGF proSAAS INT-LAMP5 Lamp5 Cerebral cortex: 70.6%, Hippocampus: 13.8%, Amygdala: 10.2% NDNF, CXCL14, AC005064.1, RELN, NMBR, LINC00298, MYH11, AC092819.3, NR2E1, SLC25A48
Cluster132 1.1917e-05 Miscellaneous NEUR VGLUT1 VGLUT2 CBLN CCK CHGA CHGB NAMPT NUCB SCG UBL VGF proSAAS 0 Cerebral cortex: 98.4%, Hippocampus: 0.8%, Midbrain: 0.8% CD53, DPP4, AC060765.1, LINC01721, AC112770.1, AL157769.1, VIPR2, PCSK1, AC016687.2, QRFPR
Cluster137 1.7584e-05 Deep-layer intratelencephalic NEUR VGLUT1 VGLUT2 CBLN CCK CHGA CHGB CRH NAMPT NUCB SCG UBL UCN VGF proSAAS 0 L5 IT Cerebral cortex: 94.4%, Basal forebrain: 2.1%, Hippocampus: 1.9% LINC02196, AC099517.1, AC079380.1, AC073578.2, ADGRL4, PKD2L1, AC021134.1, AL450352.1, TRIM22, ARHGAP15

  1. Keira JA Johnston, Mark J Adams, Barbara I Nicholl, Joey Ward, Rona J Strawbridge, Amy Ferguson, Andrew M McIntosh, Mark ES Bailey, and Daniel J Smith. Genome-wide association study of multisite chronic pain in UK Biobank. PLoS Genetics, 15(6):e1008164, 2019. URL: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008164. ↩

  2. Kimberly Siletti, Rebecca Hodge, Alejandro Mossi Albiach, Ka Wai Lee, Song-Lin Ding, Lijuan Hu, Peter Lönnerberg, Trygve Bakken, Tamara Casper, Michael Clark, and others. Transcriptomic diversity of cell types across the adult human brain. Science, 382(6667):eadd7046, 2023. URL: https://www.science.org/doi/abs/10.1126/science.add7046. ↩

  3. Kyoko Watanabe, Maša Umićević Mirkov, Christiaan A de Leeuw, Martijn P van den Heuvel, and Danielle Posthuma. Genetic mapping of cell type specificity for complex traits. Nature Communications, 10(1):3222, 2019. URL: https://www.nature.com/articles/s41467-019-11181-1. ↩