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MAGMA HBA Analysis

I applied MAGMA to the educational attainment GWAS of Lee et al.1 using scRNAseq data from the Human Brain Atlas as a reference.

In the plot below, the x-axis corresponds to HBA cluster number2, 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. I used a conditional analysis approach based on the one described in Wanatabe et al.3 to identify independent clusters. These independent clusters are labeled in plot.

edu-hba-magma

The independent clusters are listed in more detail in the table below:

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
Cluster234 1.6139e-14 Eccentric medium spiny neuron NEUR GABA CCK CHGA CHGB NAMPT NUCB PENK SCG UBL VGF proSAAS MSN-D1 Amygdala: 75.9%, Cerebral cortex: 14.6%, Thalamus: 5.4% NPFFR2, ZNF736P9Y, GABRQ, LMNTD1, EYA2, AC012078.2, AC087516.2, PCDH11Y, LINC00354, NMBR
Cluster146 1.0347e-12 Deep-layer intratelencephalic NEUR VGLUT1 VGLUT2 ADCYAP CBLN CCK CHGA CHGB NAMPT NUCB SCG UBL VGF proSAAS 0 Amygdala: 65.4%, Cerebral cortex: 33.1%, Hypothalamus: 0.8% CCN4, STPG2-AS1, AC105450.1, LINC00683, ATP10A, SNTG2, UCMA, TMEM244, FGF10, LINC02008
Cluster280 7.3007e-09 CGE interneuron NEUR GABA CCK CHGA CHGB CRH IGF NAMPT NUCB PNOC SCG UBL VIP proSAAS INT-VIP Cerebral cortex: 73.7%, Amygdala: 13.3%, Hippocampus: 7.8% AC006305.1, LINC01416, AL391832.4, LINC01905, SP8, DCN, CHRNB3, CXCL14, CHRNA7, CRH
Cluster202 4.4341e-08 Hippocampal dentate gyrus NEUR VGLUT1 CBLN CHGB GRP NAMPT NUCB UBL proSAAS DG-GRAN Hippocampus: 100.0%, Cerebral cortex: 0.0%, Amygdala: 0.0% TTR, FOLR1, LINC01697, AC097528.1, AC097487.1, AL672167.1, NTF3, AL591518.1, TARID, AJ006995.1
Cluster133 1.1749e-07 Upper-layer intratelencephalic NEUR VGLUT1 VGLUT2 ADCYAP CBLN CCK CHGA CHGB NAMPT NUCB SCG UBL VGF proSAAS 0 Cerebral cortex: 100.0%, Basal forebrain: 0.0%, Hypothalamus: 0.0% LINC02388, AC112770.1, AC092448.1, AC126182.3, VIPR2, TRPC3, AC020637.1, IGFBP2, SLC38A11, LINC02296
Cluster404 2.9387e-07 Miscellaneous NEUR VGLUT1 CBLN CCK CHGA CHGB IGF NAMPT NUCB NXPH SCG SST TAC VGF proSAAS 0 Cerebral cortex: 94.4%, Amygdala: 2.5%, Basal forebrain: 1.2% AC016687.2, AC021134.1, LINC02378, LINC02263, LINC01915, CXCL14, AL033539.2, AC004862.1, AC073578.2, LINC02306
Cluster439 6.1461e-07 Midbrain-derived inhibitory NEUR GABA CBLN CHGA CHGB IGF NAMPT NPPC NUCB NXPH SCG UBL proSAAS 0 Midbrain: 52.8%, Thalamus: 31.3%, Pons: 10.7% DMBX1, OTX2-AS1, OTX2, LINC01210, GATA3, AC008163.1, AL161757.4, LINC02055, SOX14, PRSS12

  1. James J Lee, Robbee Wedow, Aysu Okbay, Edward Kong, Omeed Maghzian, Meghan Zacher, Tuan Anh Nguyen-Viet, Peter Bowers, Julia Sidorenko, Richard Karlsson Linnér, and others. Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. Nature Genetics, 50(8):1112–1121, 2018. URL: https://www.nature.com/articles/s41588-018-0147-3. ↩

  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. ↩