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

Genome-Wide Association Meta-Analysis of Single-Nucleotide Polymorphisms and Symptomatic Venous Thromboembolism during Therapy for Acute Lymphoblastic Leukemia and Lymphoma in Caucasian Children

Research output: Contribution to journalJournal articlepeer-review


  1. Cancer-related Mutations with Local or Long-range Effects on an Allosteric Loop of p53

    Research output: Contribution to journalJournal articlepeer-review

  2. Clonal Hematopoiesis and Epigenetic Age Acceleration in Elderly Danish Twins

    Research output: Contribution to journalJournal articlepeer-review

  • Marion K Mateos
  • Morten Tulstrup
  • Michael Cj Quinn
  • Ruta Tuckuviene
  • Glenn M Marshall
  • Ramneek Gupta
  • Chelsea Mayoh
  • Benjamin O Wolthers
  • Pasquale M Barbaro
  • Ellen Ruud
  • Rosemary Sutton
  • Pasi Huttunen
  • Tamas Revesz
  • Sonata S Trakymiene
  • Draga Barbaric
  • Ulf Tedgård
  • Jodie E Giles
  • Frank Alvaro
  • Olafur G Jonsson
  • Françoise Mechinaud
  • Kadri Saks
  • Daniel Catchpoole
  • Rishi S Kotecha
  • Luciano Dalla-Pozza
  • Georgia Chenevix-Trench
  • Toby N Trahair
  • Stuart MacGregor
  • Kjeld Schmiegelow
View graph of relations

Symptomatic venous thromboembolism (VTE) occurs in five percent of children treated for acute lymphoblastic leukemia (ALL), but whether a genetic predisposition exists across different ALL treatment regimens has not been well studied.

METHODS: We undertook a genome-wide association study (GWAS) meta-analysis for VTE in consecutively treated children in the Nordic/Baltic acute lymphoblastic leukemia 2008 (ALL2008) cohort and the Australian Evaluation of Risk of ALL Treatment-Related Side-Effects (ERASE) cohort. A total of 92 cases and 1481 controls of European ancestry were included.

RESULTS: No SNPs reached genome-wide significance (p < 5 × 10-8) in either cohort. Among the top 34 single-nucleotide polymorphisms (SNPs) (p < 1 × 10-6), two loci had concordant effects in both cohorts: ALOX15B (rs1804772) (MAF: 1%; p = 3.95 × 10-7) that influences arachidonic acid metabolism and thus platelet aggregation, and KALRN (rs570684) (MAF: 1%; p = 4.34 × 10-7) that has been previously associated with risk of ischemic stroke, atherosclerosis, and early-onset coronary artery disease.

CONCLUSION: This represents the largest GWAS meta-analysis conducted to date associating SNPs to VTE in children and adolescents treated on childhood ALL protocols. Validation of these findings is needed and may then lead to patient stratification for VTE preventive interventions. As VTE hemostasis involves multiple pathways, a more powerful GWAS is needed to detect combination of variants associated with VTE.

Original languageEnglish
Issue number5
Publication statusPublished - 19 May 2020

ID: 62100548