{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:15:00Z","timestamp":1790957700218,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006398","name":"Roswell Park Alliance Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006398","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03 CA223730"],"award-info":[{"award-number":["R03 CA223730"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA16056"],"award-info":[{"award-number":["P30 CA16056"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Bone toxicities are common among paediatric patients treated for acute lymphoblastic leukaemia (ALL) with potentially major negative impact on patients' quality of life. To identify the underlying genetic contributors, we conducted a genome\u2010wide association study (GWAS) and a transcriptome\u2010wide association study (TWAS) in 260 patients of European\u2010descent from the DFCI 05\u2013001 ALL trial, with validation in 101 patients of European\u2010descent from the DFCI 11\u2013001 ALL trial. We identified a significant association between rs844882 on chromosome 20 and bone toxicities in the DFCI 05\u2013001 trial (<jats:italic>p<\/jats:italic>\u2009=\u20091.7\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>). In DFCI 11\u2013001 trial, we observed a consistent trend of this variant with fracture. The variant was an eQTL for two nearby genes, <jats:italic>CD93<\/jats:italic> and <jats:italic>THBD<\/jats:italic>. In TWAS, genetically predicted <jats:italic>ACAD9<\/jats:italic> expression was associated with an increased risk of bone toxicities, which was confirmed by meta\u2010analysis of the two cohorts (meta\u2010<jats:italic>p<\/jats:italic>\u2009=\u20092.4\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>). In addition, a polygenic risk score of heel quantitative ultrasound speed of sound was associated with fracture risk in both cohorts (meta\u2010<jats:italic>p<\/jats:italic>\u2009=\u20092.3\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>). Our findings highlight the genetic influence on treatment\u2010related bone toxicities in this patient population. The genes we identified in our study provide new biological insights into the development of bone adverse events related to ALL treatment.<\/jats:p>","DOI":"10.1111\/bjh.19696","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T23:08:15Z","timestamp":1723676895000},"page":"1889-1898","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genome\u2010wide study identifies novel genes associated with bone toxicities in children with acute lymphoblastic leukaemia"],"prefix":"10.1111","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2516-6675","authenticated-orcid":false,"given":"Qianqian","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Nambiar","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Schultz","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8776-2125","authenticated-orcid":false,"given":"Shuyi","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Flamand","sequence":"additional","affiliation":[{"name":"Department of Data Science Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Department of Data Science Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Cole","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology Rutgers Cancer Institute of New Jersey  New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Gennarini","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology, Oncology and Cellular Therapy, Children's Hospital at Montefiore Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian H.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Pathology Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine M.","family":"Kahn","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology\/Stem Cell Transplantation Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena J.","family":"Ladas","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology\/Stem Cell Transplantation Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma H.","family":"Athale","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thai","family":"Hoa\u00a0Tran","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Charles\u2010Bruneau Cancer Center, CHU Sainte\u2010Justine University of Montreal  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Michon","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology Centre Hospitalier Universitaire de Qu\u00e9bec  Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer J. G.","family":"Welch","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\u2010Oncology, Hasbro Children's Hospital Warren Alpert Medical School of Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen E.","family":"Sallan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana\u2010Farber Cancer Institute and Division of Pediatric Hematology\u2010Oncology Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis B.","family":"Silverman","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana\u2010Farber Cancer Institute and Division of Pediatric Hematology\u2010Oncology Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1473-3937","authenticated-orcid":false,"given":"Kara M.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology Roswell Park Comprehensive Cancer Center  Buffalo New York USA"},{"name":"Jacobs School of Medicine and Biomedical Sciences University at Buffalo  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Cancer Prevention and Control Roswell Park Comprehensive Cancer Center  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003060"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650110414"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2249"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.446"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60599-1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-021-00143-3"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.04.005"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003152"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008471"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-10-673848"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-05-643601"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-311969"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00363-0"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V126.23.248.248"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018016584"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03692"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1847"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3656"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3643"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00783-5"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15421-7"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq340"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3367"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.155192.113"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24277"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab186"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr654"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071042"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12041140"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks959"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-12-768994"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407008101"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2009.05.001"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.6065\/apem.2020.25.1.1"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24040"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18093"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abc8922"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI97459"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-3636"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222212417"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7136"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0625-7"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00535"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-015-1442-0"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0185(20000501)259:1<97::AID-AR11>3.0.CO;2-O"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(99)00076-3"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-022-00188-y"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2014.2508"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-70440-0"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv074"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.090202"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocd.2015.10.002"},{"key":"e_1_2_8_55_1","article-title":"Vitamin D deficiency in childhood acute lymphoblastic leukemia\/lymphoma: results of DFCI 11\u2013001","volume":"66","author":"Gotti GPM","year":"2019","journal-title":"Pediatr Blood Cancer"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.19696","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T08:38:48Z","timestamp":1758098328000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.19696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,14]]},"references-count":54,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/bjh.19696"],"URL":"https:\/\/doi.org\/10.1111\/bjh.19696","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,14]]},"assertion":[{"value":"2024-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}