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We describe here the GenLEA project, which was established to investigate genetic determinants of long\u2010term complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>GenLEA builds on the French LEA cohort, which prospectively follows acute leukemia survivors since 2004 through standardized dedicated consultations every 2 to 4 years. Patients were selected from the nested CryoLEA biobank. Cases were defined as survivors with at least one of four major complications (anthracycline\u2010related cardiomyopathy, secondary malignant neoplasms, metabolic syndrome, or osteonecrosis) while controls were survivors without these complications, selected with the objective of a 1:3 case\u2010to\u2010control ratio. Genetic data were generated using genome\u2010wide genotyping and whole\u2010exome sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After quality control, 743 patients were included for analyses (241 cases and 502 controls). Fifty\u2010one percent were male with a median age at diagnosis of 7.3 years (IQR 3.9\u201313.0), and median follow\u2010up reached 14 years (IQR 7.9\u201319.8). Among the cases, 44 had cardiomyopathy, 50 osteonecrosis, 37 secondary malignant neoplasms, and 163 metabolic syndrome. Planned analyses include genome\u2010wide association studies (GWAS) and downstream analyses such as transcriptome\u2010wide association studies (TWAS) and Mendelian randomization on genotyping data, as well as gene\u2010based tests on exome sequencing data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Perspectives<\/jats:title>\n                    <jats:p>By integrating these approaches with high\u2010quality clinical information, GenLEA offers a unique opportunity to identify molecular determinants of late complications after childhood acute leukemia. This collaborative resource will support replication efforts, meta\u2010analyses, and ultimately the development of personalized long\u2010term follow\u2010up strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/1545-5017.70027","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T06:55:39Z","timestamp":1767596139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genomics of Long\u2010Term Complications of Childhood Leukemia: Rationale and Design of the GenLEA Study"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2590-5577","authenticated-orcid":false,"given":"Mathilde","family":"Veneziano\u2010Broccia","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology, Immunology and Oncology, La Timone Children's Hospital, APHM, INSERM, INRAe, C2VN Aix Marseille Universit\u00e9  Marseille 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