Skip to content

MAGMA Analysis of RBC Volume

I applied the MAGMA pipeline to summary statistics from a GWAS of red blood cell (RBC) volume from the Million Veterans Program1. I incorporated tissue-specific RNAseq data from GTEx2 to try to link genes associated with RBC volume to specific tissues.

Gene set/ Gene property analysis

The graph below shows the significant cells/tissues when MAGMA gene property analysis applied to the RBC volume GWAS using reference data from the GTEx project:

rbc-bar-magma

The presence of "whole blood" is intuitive. The other four significant tissues are EBV-transformed lymphocytes, the spleen, and "Lymphode aggregate" from the small intestine. The significance of these white-blood-cell-related tissues might be explained by their similarity to erythrocytes. Erythrocytes and leukocytes share a common lineage, descending from haematopoietic stem cells (see Figure below). Thus it could be that MAGMA is picking up genes that play a role in all myeloid cells.

haemopoetic-cells

Figure: By A. Rad and M. Häggström. CC-BY-SA 3.0 license

  1. Anurag Verma, Jennifer E Huffman, Alex Rodriguez, Mitchell Conery, Molei Liu, Yuk-Lam Ho, Youngdae Kim, David A Heise, Lindsay Guare, Vidul Ayakulangara Panickan, and others. Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. Science, 385(6706):eadj1182, 2024. URL: https://www.science.org/doi/10.1126/science.adj1182. ↩

  2. 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. ↩