Exome chip analyses identify genes affecting mortality after HLA-matched unrelated-donor blood and marrow transplantation
Zhu, Q., Yan, L., Liu, Q., Zhang, C., Wei, L., Hu, Q., Preus, L., Clay-Gilmour, A. I., Onel, K., Stram, D. O., Pooler, L., Sheng, X., Haiman, C. A., Zhu, X., Spellman, S. R., Pasquini, M., McCarthy, P. L., Liu, S., Hahn, T., Sucheston-Campbell, L. E.
American Society of Hematology (ASH)
Published 2018
American Society of Hematology (ASH)
Published 2018
| Publication Date: |
2018-06-01
|
|---|---|
| Publisher: |
American Society of Hematology (ASH)
|
| Print ISSN: |
0006-4971
|
| Electronic ISSN: |
1528-0020
|
| Topics: |
Biology
Medicine
|
| Keywords: |
Transplantation
|
| Published by: |
| _version_ | 1836398951882817536 |
|---|---|
| autor | Zhu, Q., Yan, L., Liu, Q., Zhang, C., Wei, L., Hu, Q., Preus, L., Clay-Gilmour, A. I., Onel, K., Stram, D. O., Pooler, L., Sheng, X., Haiman, C. A., Zhu, X., Spellman, S. R., Pasquini, M., McCarthy, P. L., Liu, S., Hahn, T., Sucheston-Campbell, L. E. |
| beschreibung | Although survival outcomes have significantly improved, up to 40% of patients die within 1 year of HLA-matched unrelated-donor blood and marrow transplantation (BMT). To identify non-HLA genetic contributors to mortality after BMT, we performed the first exome-wide association study in the DISCOVeRY-BMT cohorts using the Illumina HumanExome BeadChip. This study includes 2473 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome and 2221 10/10 HLA-matched donors treated from 2000 to 2011. Single-variant and gene-level analyses were performed on overall survival (OS), transplantation-related mortality (TRM), and disease-related mortality (DRM). Genotype mismatches between recipients and donors in a rare nonsynonymous variant of testis-expressed gene TEX38 significantly increased risk of TRM, which was more dramatic when either the recipient or donor was female. Using the SKAT-O test to evaluate gene-level effects, variant genotypes of OR51D1 in recipients were significantly associated with OS and TRM. In donors, 4 ( ALPP , EMID1 , SLC44A5 , LRP1 ), 1 ( HHAT ), and 2 genes ( LYZL4 , NT5E ) were significantly associated with OS, TRM, and DRM, respectively. Inspection of NT5E crystal structures showed 4 of the associated variants affected the enzyme structure and likely decreased the catalytic efficiency of the enzyme. Further confirmation of these findings and additional functional studies may provide individualized risk prediction and prognosis, as well as alternative donor selection strategies. |
| citation_standardnr | 6272597 |
| datenlieferant | ipn_articles |
| feed_id | 310 |
| feed_publisher | American Society of Hematology (ASH) |
| feed_publisher_url | http://www.hematology.org/ |
| insertion_date | 2018-06-01 |
| journaleissn | 1528-0020 |
| journalissn | 0006-4971 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | American Society of Hematology (ASH) |
| quelle | Blood |
| relation | http://www.bloodjournal.org/cgi/content/short/131/22/2490?rss=1 |
| schlagwort | Transplantation |
| search_space | articles |
| shingle_author_1 | Zhu, Q., Yan, L., Liu, Q., Zhang, C., Wei, L., Hu, Q., Preus, L., Clay-Gilmour, A. I., Onel, K., Stram, D. O., Pooler, L., Sheng, X., Haiman, C. A., Zhu, X., Spellman, S. R., Pasquini, M., McCarthy, P. L., Liu, S., Hahn, T., Sucheston-Campbell, L. E. |
| shingle_author_2 | Zhu, Q., Yan, L., Liu, Q., Zhang, C., Wei, L., Hu, Q., Preus, L., Clay-Gilmour, A. I., Onel, K., Stram, D. O., Pooler, L., Sheng, X., Haiman, C. A., Zhu, X., Spellman, S. R., Pasquini, M., McCarthy, P. L., Liu, S., Hahn, T., Sucheston-Campbell, L. E. |
| shingle_author_3 | Zhu, Q., Yan, L., Liu, Q., Zhang, C., Wei, L., Hu, Q., Preus, L., Clay-Gilmour, A. I., Onel, K., Stram, D. O., Pooler, L., Sheng, X., Haiman, C. A., Zhu, X., Spellman, S. R., Pasquini, M., McCarthy, P. L., Liu, S., Hahn, T., Sucheston-Campbell, L. E. |
| shingle_author_4 | Zhu, Q., Yan, L., Liu, Q., Zhang, C., Wei, L., Hu, Q., Preus, L., Clay-Gilmour, A. I., Onel, K., Stram, D. O., Pooler, L., Sheng, X., Haiman, C. A., Zhu, X., Spellman, S. R., Pasquini, M., McCarthy, P. L., Liu, S., Hahn, T., Sucheston-Campbell, L. E. |
| shingle_catch_all_1 | Exome chip analyses identify genes affecting mortality after HLA-matched unrelated-donor blood and marrow transplantation Transplantation Although survival outcomes have significantly improved, up to 40% of patients die within 1 year of HLA-matched unrelated-donor blood and marrow transplantation (BMT). To identify non-HLA genetic contributors to mortality after BMT, we performed the first exome-wide association study in the DISCOVeRY-BMT cohorts using the Illumina HumanExome BeadChip. This study includes 2473 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome and 2221 10/10 HLA-matched donors treated from 2000 to 2011. Single-variant and gene-level analyses were performed on overall survival (OS), transplantation-related mortality (TRM), and disease-related mortality (DRM). Genotype mismatches between recipients and donors in a rare nonsynonymous variant of testis-expressed gene TEX38 significantly increased risk of TRM, which was more dramatic when either the recipient or donor was female. Using the SKAT-O test to evaluate gene-level effects, variant genotypes of OR51D1 in recipients were significantly associated with OS and TRM. In donors, 4 ( ALPP , EMID1 , SLC44A5 , LRP1 ), 1 ( HHAT ), and 2 genes ( LYZL4 , NT5E ) were significantly associated with OS, TRM, and DRM, respectively. Inspection of NT5E crystal structures showed 4 of the associated variants affected the enzyme structure and likely decreased the catalytic efficiency of the enzyme. Further confirmation of these findings and additional functional studies may provide individualized risk prediction and prognosis, as well as alternative donor selection strategies. Zhu, Q., Yan, L., Liu, Q., Zhang, C., Wei, L., Hu, Q., Preus, L., Clay-Gilmour, A. I., Onel, K., Stram, D. O., Pooler, L., Sheng, X., Haiman, C. A., Zhu, X., Spellman, S. R., Pasquini, M., McCarthy, P. L., Liu, S., Hahn, T., Sucheston-Campbell, L. E. American Society of Hematology (ASH) 0006-4971 00064971 1528-0020 15280020 |
| shingle_catch_all_2 | Exome chip analyses identify genes affecting mortality after HLA-matched unrelated-donor blood and marrow transplantation Transplantation Although survival outcomes have significantly improved, up to 40% of patients die within 1 year of HLA-matched unrelated-donor blood and marrow transplantation (BMT). To identify non-HLA genetic contributors to mortality after BMT, we performed the first exome-wide association study in the DISCOVeRY-BMT cohorts using the Illumina HumanExome BeadChip. This study includes 2473 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome and 2221 10/10 HLA-matched donors treated from 2000 to 2011. Single-variant and gene-level analyses were performed on overall survival (OS), transplantation-related mortality (TRM), and disease-related mortality (DRM). Genotype mismatches between recipients and donors in a rare nonsynonymous variant of testis-expressed gene TEX38 significantly increased risk of TRM, which was more dramatic when either the recipient or donor was female. Using the SKAT-O test to evaluate gene-level effects, variant genotypes of OR51D1 in recipients were significantly associated with OS and TRM. In donors, 4 ( ALPP , EMID1 , SLC44A5 , LRP1 ), 1 ( HHAT ), and 2 genes ( LYZL4 , NT5E ) were significantly associated with OS, TRM, and DRM, respectively. Inspection of NT5E crystal structures showed 4 of the associated variants affected the enzyme structure and likely decreased the catalytic efficiency of the enzyme. Further confirmation of these findings and additional functional studies may provide individualized risk prediction and prognosis, as well as alternative donor selection strategies. Zhu, Q., Yan, L., Liu, Q., Zhang, C., Wei, L., Hu, Q., Preus, L., Clay-Gilmour, A. I., Onel, K., Stram, D. O., Pooler, L., Sheng, X., Haiman, C. A., Zhu, X., Spellman, S. R., Pasquini, M., McCarthy, P. L., Liu, S., Hahn, T., Sucheston-Campbell, L. E. American Society of Hematology (ASH) 0006-4971 00064971 1528-0020 15280020 |
| shingle_catch_all_3 | Exome chip analyses identify genes affecting mortality after HLA-matched unrelated-donor blood and marrow transplantation Transplantation Although survival outcomes have significantly improved, up to 40% of patients die within 1 year of HLA-matched unrelated-donor blood and marrow transplantation (BMT). To identify non-HLA genetic contributors to mortality after BMT, we performed the first exome-wide association study in the DISCOVeRY-BMT cohorts using the Illumina HumanExome BeadChip. This study includes 2473 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome and 2221 10/10 HLA-matched donors treated from 2000 to 2011. Single-variant and gene-level analyses were performed on overall survival (OS), transplantation-related mortality (TRM), and disease-related mortality (DRM). Genotype mismatches between recipients and donors in a rare nonsynonymous variant of testis-expressed gene TEX38 significantly increased risk of TRM, which was more dramatic when either the recipient or donor was female. Using the SKAT-O test to evaluate gene-level effects, variant genotypes of OR51D1 in recipients were significantly associated with OS and TRM. In donors, 4 ( ALPP , EMID1 , SLC44A5 , LRP1 ), 1 ( HHAT ), and 2 genes ( LYZL4 , NT5E ) were significantly associated with OS, TRM, and DRM, respectively. Inspection of NT5E crystal structures showed 4 of the associated variants affected the enzyme structure and likely decreased the catalytic efficiency of the enzyme. Further confirmation of these findings and additional functional studies may provide individualized risk prediction and prognosis, as well as alternative donor selection strategies. Zhu, Q., Yan, L., Liu, Q., Zhang, C., Wei, L., Hu, Q., Preus, L., Clay-Gilmour, A. I., Onel, K., Stram, D. O., Pooler, L., Sheng, X., Haiman, C. A., Zhu, X., Spellman, S. R., Pasquini, M., McCarthy, P. L., Liu, S., Hahn, T., Sucheston-Campbell, L. E. American Society of Hematology (ASH) 0006-4971 00064971 1528-0020 15280020 |
| shingle_catch_all_4 | Exome chip analyses identify genes affecting mortality after HLA-matched unrelated-donor blood and marrow transplantation Transplantation Although survival outcomes have significantly improved, up to 40% of patients die within 1 year of HLA-matched unrelated-donor blood and marrow transplantation (BMT). To identify non-HLA genetic contributors to mortality after BMT, we performed the first exome-wide association study in the DISCOVeRY-BMT cohorts using the Illumina HumanExome BeadChip. This study includes 2473 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome and 2221 10/10 HLA-matched donors treated from 2000 to 2011. Single-variant and gene-level analyses were performed on overall survival (OS), transplantation-related mortality (TRM), and disease-related mortality (DRM). Genotype mismatches between recipients and donors in a rare nonsynonymous variant of testis-expressed gene TEX38 significantly increased risk of TRM, which was more dramatic when either the recipient or donor was female. Using the SKAT-O test to evaluate gene-level effects, variant genotypes of OR51D1 in recipients were significantly associated with OS and TRM. In donors, 4 ( ALPP , EMID1 , SLC44A5 , LRP1 ), 1 ( HHAT ), and 2 genes ( LYZL4 , NT5E ) were significantly associated with OS, TRM, and DRM, respectively. Inspection of NT5E crystal structures showed 4 of the associated variants affected the enzyme structure and likely decreased the catalytic efficiency of the enzyme. Further confirmation of these findings and additional functional studies may provide individualized risk prediction and prognosis, as well as alternative donor selection strategies. Zhu, Q., Yan, L., Liu, Q., Zhang, C., Wei, L., Hu, Q., Preus, L., Clay-Gilmour, A. I., Onel, K., Stram, D. O., Pooler, L., Sheng, X., Haiman, C. A., Zhu, X., Spellman, S. R., Pasquini, M., McCarthy, P. L., Liu, S., Hahn, T., Sucheston-Campbell, L. E. American Society of Hematology (ASH) 0006-4971 00064971 1528-0020 15280020 |
| shingle_title_1 | Exome chip analyses identify genes affecting mortality after HLA-matched unrelated-donor blood and marrow transplantation |
| shingle_title_2 | Exome chip analyses identify genes affecting mortality after HLA-matched unrelated-donor blood and marrow transplantation |
| shingle_title_3 | Exome chip analyses identify genes affecting mortality after HLA-matched unrelated-donor blood and marrow transplantation |
| shingle_title_4 | Exome chip analyses identify genes affecting mortality after HLA-matched unrelated-donor blood and marrow transplantation |
| timestamp | 2025-06-30T23:35:15.007Z |
| titel | Exome chip analyses identify genes affecting mortality after HLA-matched unrelated-donor blood and marrow transplantation |
| titel_suche | Exome chip analyses identify genes affecting mortality after HLA-matched unrelated-donor blood and marrow transplantation |
| topic | W WW-YZ |
| uid | ipn_articles_6272597 |