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MAGMA GTEx

I applied MAGMA1 to the Alzheimer's GWAS of Bellenguez et al.2 using a reference dataset derived from GTEx bulk RNAseq data3. The gene-property analysis results are plotted below.

magma-alz-gtex

Three of the four significant tissues types (Whole blood, Spleen, Ileum Lymphode aggregate) are immune-related, which is consistent with theories of Alzheimer's as an immune-related disease. How to interpret "Liver portal tract" is less obvious.

  1. Christiaan A De Leeuw, Joris M Mooij, Tom Heskes, and Danielle Posthuma. MAGMA: generalized gene-set analysis of GWAS data. PLoS Computational Biology, 11(4):e1004219, 2015. URL: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004219. ↩

  2. Céline Bellenguez, Fahri Küçükali, Iris E Jansen, Luca Kleineidam, Sonia Moreno-Grau, Najaf Amin, Adam C Naj, Rafael Campos-Martin, Benjamin Grenier-Boley, Victor Andrade, and others. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nature Genetics, 54(4):412–436, 2022. URL: https://www.nature.com/articles/s41588-022-01024-z. ↩

  3. GTEx Consortium. The GTEx consortium atlas of genetic regulatory effects across human tissues. Science, 369(6509):1318–1330, 2020. URL: https://www.science.org/doi/full/10.1126/science.aaz1776. ↩