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

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Harvard

Jarvis, KB, Nielsen, RL, Gupta, R, Hede, FD, Huttunen, P, Jónsson, ÓG, Rank, CU, Ranta, S, Saks, K, Trakymiene, SS, Tuckuviene, R, Tulstrup, M, Ruud, E, Schmiegelow, K, LeBlanc, M & INVENT consortium 2020, 'Polygenic risk score-analysis of thromboembolism in patients with acute lymphoblastic leukemia', Thrombosis Research, bind 196, s. 15-20. https://doi.org/10.1016/j.thromres.2020.08.015

APA

Jarvis, K. B., Nielsen, R. L., Gupta, R., Hede, F. D., Huttunen, P., Jónsson, Ó. G., Rank, C. U., Ranta, S., Saks, K., Trakymiene, S. S., Tuckuviene, R., Tulstrup, M., Ruud, E., Schmiegelow, K., LeBlanc, M., & INVENT consortium (2020). Polygenic risk score-analysis of thromboembolism in patients with acute lymphoblastic leukemia. Thrombosis Research, 196, 15-20. https://doi.org/10.1016/j.thromres.2020.08.015

CBE

Jarvis KB, Nielsen RL, Gupta R, Hede FD, Huttunen P, Jónsson ÓG, Rank CU, Ranta S, Saks K, Trakymiene SS, Tuckuviene R, Tulstrup M, Ruud E, Schmiegelow K, LeBlanc M, INVENT consortium. 2020. Polygenic risk score-analysis of thromboembolism in patients with acute lymphoblastic leukemia. Thrombosis Research. 196:15-20. https://doi.org/10.1016/j.thromres.2020.08.015

MLA

Vancouver

Author

Jarvis, Kirsten Brunsvig ; Nielsen, Rikke Linnemann ; Gupta, Ramneek ; Hede, Freja Dahl ; Huttunen, Pasi ; Jónsson, Ólafur Gísli ; Rank, Cecilie Utke ; Ranta, Susanna ; Saks, Kadri ; Trakymiene, Sonata Saulyte ; Tuckuviene, Ruta ; Tulstrup, Morten ; Ruud, Ellen ; Schmiegelow, Kjeld ; LeBlanc, Marissa ; INVENT consortium. / Polygenic risk score-analysis of thromboembolism in patients with acute lymphoblastic leukemia. I: Thrombosis Research. 2020 ; Bind 196. s. 15-20.

Bibtex

@article{89fdc1ad052344ac90d57276aa6afefc,
title = "Polygenic risk score-analysis of thromboembolism in patients with acute lymphoblastic leukemia",
abstract = "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.",
keywords = "Acute lymphoblastic leukemia, Polygenic risk score, Thromboembolism",
author = "Jarvis, {Kirsten Brunsvig} and Nielsen, {Rikke Linnemann} and Ramneek Gupta and Hede, {Freja Dahl} and Pasi Huttunen and J{\'o}nsson, {{\'O}lafur G{\'i}sli} and Rank, {Cecilie Utke} and Susanna Ranta and Kadri Saks and Trakymiene, {Sonata Saulyte} and Ruta Tuckuviene and Morten Tulstrup and Ellen Ruud and Kjeld Schmiegelow and Marissa LeBlanc and {INVENT consortium}",
note = "Copyright {\textcopyright} 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.",
year = "2020",
month = dec,
doi = "10.1016/j.thromres.2020.08.015",
language = "English",
volume = "196",
pages = "15--20",
journal = "Thrombosis Research",
issn = "0049-3848",
publisher = "Pergamon",

}

RIS

TY - JOUR

T1 - Polygenic risk score-analysis of thromboembolism in patients with acute lymphoblastic leukemia

AU - Jarvis, Kirsten Brunsvig

AU - Nielsen, Rikke Linnemann

AU - Gupta, Ramneek

AU - Hede, Freja Dahl

AU - Huttunen, Pasi

AU - Jónsson, Ólafur Gísli

AU - Rank, Cecilie Utke

AU - Ranta, Susanna

AU - Saks, Kadri

AU - Trakymiene, Sonata Saulyte

AU - Tuckuviene, Ruta

AU - Tulstrup, Morten

AU - Ruud, Ellen

AU - Schmiegelow, Kjeld

AU - LeBlanc, Marissa

AU - INVENT consortium

N1 - Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2020/12

Y1 - 2020/12

N2 - 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.

AB - 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.

KW - Acute lymphoblastic leukemia

KW - Polygenic risk score

KW - Thromboembolism

U2 - 10.1016/j.thromres.2020.08.015

DO - 10.1016/j.thromres.2020.08.015

M3 - Journal article

C2 - 32818716

VL - 196

SP - 15

EP - 20

JO - Thrombosis Research

JF - Thrombosis Research

SN - 0049-3848

ER -

ID: 60774469