Journal article
Genome-wide association meta-analysis of single-nucleotide polymorphisms and symptomatic venous thromboembolism during therapy for acute lymphoblastic leukemia and lymphoma in caucasian children
University of New South Wales1
University of Helsinki2
Women's and Children's Hospital Adelaide3
Vilnius University4
Sydney Children's Hospital5
Lund University6
University of Newcastle7
Landspitali University Hospital8
Hôpital Robert Debré AP-HP9
University Children’s Hospital Tallinn10
Curtin University11
University of Copenhagen12
Queensland Institute of Medical Research13
Aalborg University14
Department of Health Technology, Technical University of Denmark15
Bioinformatics, Department of Health Technology, Technical University of Denmark16
Disease Data Intelligence, Bioinformatics, Department of Health Technology, Technical University of Denmark17
University of Sydney18
University of Oslo19
...and 9 moreSymptomatic 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.
Language: | English |
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Publisher: | MDPI |
Year: | 2020 |
Pages: | 1285 |
ISSN: | 20726694 |
Types: | Journal article |
DOI: | 10.3390/cancers12051285 |
ORCIDs: | Gupta, Ramneek , 0000-0002-7444-7652 , 0000-0002-6398-3046 , 0000-0002-2695-7244 , 0000-0002-0731-1245 , 0000-0003-2828-8758 , 0000-0001-5836-1413 , 0000-0003-1836-4075 , 0000-0002-3295-228X and 0000-0002-0829-4993 |