Replication and validation of genetic polymorphisms associated with survival after allogeneic blood or marrow transplant
Multiple candidate gene-association studies of non-HLA single-nucleotide polymorphisms (SNPs) and outcomes after blood or marrow transplant (BMT) have been conducted. We identified 70 publications reporting 45 SNPs in 36 genes significantly associated with disease-related mortality, progression-free survival, transplant-related mortality, and/or overall survival after BMT. Replication and validation of these SNP associations were performed using DISCOVeRY-BMT (Determining the Influence of Susceptibility COnveying Variants Related to one-Year mortality after BMT), a well-powered genome-wide association study consisting of 2 cohorts, totaling 2888 BMT recipients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome, and their HLA-matched unrelated donors, reported to the Center for International Blood and Marrow Transplant Research. Gene-based tests were used to assess the aggregate effect of SNPs on outcome. None of the previously reported significant SNPs replicated at P < .05 in DISCOVeRY-BMT. Validation analyses showed association with one previously reported donor SNP at P < .05 and survival; more associations would be anticipated by chance alone. No gene-based tests were significant at P < .05. Functional annotation with publicly available data shows these candidate SNPs most likely do not have biochemical function; only 13% of candidate SNPs correlate with gene expression or are predicted to impact transcription factor binding. O...
Source: Blood - Category: Hematology Authors: Karaesmen, E., Rizvi, A. A., Preus, L. M., McCarthy, P. L., Pasquini, M. C., Onel, K., Zhu, X., Spellman, S., Haiman, C. A., Stram, D. O., Pooler, L., Sheng, X., Zhu, Q., Yan, L., Liu, Q., Hu, Q., Webb, A., Brock, G., Clay-Gilmour, A. I., Battaglia, S., T Tags: Transplantation Source Type: research
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