Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Polygenic risk score-analysis of thromboembolism in patients with acute lymphoblastic leukemia

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Thromboembolic events related to atrial fibrillation during the COVID-19 epidemic in Denmark

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Comparative effectiveness of oral anticoagulants in venous thromboembolism: GARFIELD-VTE

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Hemoglobin concentration and risk of arterial and venous thrombosis in 1.5 million Swedish and Danish blood donors

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

INTRODUCTION: Thromboembolism (TE) is a common and serious toxicity of acute lymphoblastic leukemia (ALL) treatment, but studies of genetic predisposition have been underpowered with conflicting results. We tested whether TE in ALL and TE in the general adult population have a shared genetic etiology.

MATERIALS AND METHODS: We prospectively registered TE events and collected germline DNA in patients 1.0-45.9 years in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 study (7/2008-7/2016). Based on summary statistics from two large genome-wide association studies (GWAS) on venous TE in adults (the International Network of VENous Thromboembolism Clinical Research Networks (INVENT) consortium and the UK Biobank), we performed polygenic risk score (PRS) analysis on TE development in the NOPHO cohort, progressively expanding the PRS by increasing the p-value threshold of single nucleotide polymorphism (SNP) inclusion.

RESULTS AND CONCLUSION: Eighty-nine of 1252 patients with ALL developed TE, 2.5 year cumulative incidence 7.2%. PRS of genome-wide significant SNPs from the INVENT and UK Biobank data were not significantly associated with TE, HR 1.16 (p 0.14) and 1.02 (p 0.86), respectively. Expanding PRS by increasing p-value threshold did not reveal polygenic overlap. However, subgroup analysis of adolescents 10.0-17.9 years (n = 231), revealed significant polygenic overlap with the INVENT GWAS. The best fit PRS, including 16,144 SNPs, was associated with TE with HR 1.76 (95% CI 1.23-2.52, empirical p-value 0.02). Our results support an underlying genetic predisposition for TE in adolescents with ALL and should be explored further in future TE risk prediction models.

Translated title of the contributionPolygenetisk risiko score analyse af tromboemboli hos patienter med akut lymfoblastær leukæmi
Original languageEnglish
JournalThrombosis Research
Volume196
Pages (from-to)15-20
Number of pages6
ISSN0049-3848
DOIs
Publication statusPublished - Dec 2020

    Research areas

  • Acute lymphoblastic leukemia, Polygenic risk score, Thromboembolism

ID: 60774469