Faculty Collaboration Database

Whole Blood Transcriptomic Analysis of Sickle Cell Trait. Eur J Haematol 2026 May;116(5):535-544

Date

01/13/2026

Pubmed ID

41528117

Pubmed Central ID

PMC13050677

DOI

10.1111/ejh.70114

Scopus ID

2-s2.0-105027402906 (requires institutional sign-in at Scopus site)

Abstract

Sickle cell trait (SCT) is the heterozygous carrier state for the HBB missense variant which causes sickle cell disease (SCD). SCT has been associated with increased risk of venous thromboembolism and chronic kidney disease as well as alterations in clinical laboratory parameters. To investigate differential gene expression in SCT, we used RNA sequencing of whole blood samples collected from 805 African American female participants (143 SCT; 660 controls) from the Women's Health Initiative Long Life Study (mean age = 76). We identified 226 differentially expressed genes (DEGs) in SCT compared to non-carriers (FDR < 0.05). Enriched pathways included those related to erythropoiesis, hemoglobin synthesis, and proteasomal degradation. Many of the SCT-associated DEGs were previously reported as differentially expressed in blood from individuals with SCD. Among the DEGs associated with SCT, we observed enrichment of upregulated ubiquitin-related genes normally downregulated during the later stages of erythroid differentiation, a pattern previously reported in SCD. Several of the SCT-associated DEGs highlight mechanisms that potentially link hemolysis or erythropoiesis to hypoxic kidney tubular injury. Future investigation of these genes using single cell transcriptomic analysis in relevant tissues may be useful in understanding mechanisms for adverse health outcomes in individuals with SCT.

Author List

Johnson M, Cai Y, Vasconcelos AG, Orchard P, Auer PL, Lettre G, Wen J, Franceschini N, Kooperberg C, Sun W, Hsu L, Raffield LM, Reiner AP

Author

Paul L. Auer PhD Professor in the Data Science Institute department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Biomarkers
Erythropoiesis
Female
Gene Expression Profiling
Gene Expression Regulation
Humans
Sickle Cell Trait
Transcriptome