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Genome-Wide Association Analyses Identify Variants in Associated With Acute Myeloid Leukemia and Myelodysplastic Syndrome Susceptibility. | LitMetric

AI Article Synopsis

  • Researchers investigated how common genetic variations may influence the risk of developing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in a large study involving 2,309 patients and 2,814 controls.
  • Using a statistical analysis method called ASSET, they found that a specific genetic variant (T allele at s12203592) is linked to a higher risk of both AML and MDS.
  • Their findings indicate that increased gene expression related to this genetic variation significantly raises the risk of these diseases, highlighting the importance of genetics in understanding AML and MDS susceptibility.

Article Abstract

The role of common genetic variation in susceptibility to acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS), a group of rare clonal hematologic disorders characterized by dysplastic hematopoiesis and high mortality, remains unclear. We performed AML and MDS genome-wide association studies (GWAS) in the DISCOVeRY-BMT cohorts (2,309 cases and 2,814 controls). Association analysis based on subsets (ASSET) was used to conduct a summary statistics SNP-based analysis of MDS and AML subtypes. For each AML and MDS case and control we used PrediXcan to estimate the component of gene expression determined by their genetic profile and correlate this imputed gene expression level with risk of developing disease in a transcriptome-wide association study (TWAS). ASSET identified an increased risk for AML and MDS (OR = 1.38, 95% CI, 1.26-1.51, Pmeta = 2.8 × 10) in patients carrying the T allele at s12203592 in (), a transcription factor which regulates myeloid and lymphoid hematopoietic differentiation. Our TWAS analyses showed increased gene expression is associated with increased risk of AML and MDS (OR = 3.90, 95% CI, 2.36-6.44, Pmeta = 1.0 × 10). The identification of by both GWAS and TWAS contributes valuable insight on the role of genetic variation in AML and MDS susceptibility.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248805PMC
http://dx.doi.org/10.3389/fgene.2021.554948DOI Listing

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