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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\u2009=\u200976). We identified 226 differentially expressed genes (DEGs) in SCT compared to non\u2010carriers (FDR &lt;\u20090.05). Enriched pathways included those related to erythropoiesis, hemoglobin synthesis, and proteasomal degradation. Many of the SCT\u2010associated 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\u2010related genes normally downregulated during the later stages of erythroid differentiation, a pattern previously reported in SCD. Several of the SCT\u2010associated 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.\n                  <\/jats:p>","DOI":"10.1111\/ejh.70114","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T07:00:28Z","timestamp":1768374028000},"page":"535-544","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Whole Blood Transcriptomic Analysis of Sickle Cell Trait"],"prefix":"10.1111","volume":"116","author":[{"given":"Mari","family":"Johnson","sequence":"first","affiliation":[{"name":"Division of Public Health Sciences Fred Hutchinson Cancer Center  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanwei","family":"Cai","sequence":"additional","affiliation":[{"name":"Division of Public Health Sciences Fred Hutchinson Cancer Center  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Gabriela","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Orchard","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul L.","family":"Auer","sequence":"additional","affiliation":[{"name":"Joseph J. 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