Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Wei-Yu Lin; Sarah E Fordham; Eric Hungate; Nicola J Sunter; Claire Elstob; Yaobo Xu; Catherine Park; Anne Quante; Konstantin Strauch; Christian Gieger; Andrew Skol; Thahira Rahman; Lara Sucheston-Campbell; Junke Wang; Theresa Hahn; Alyssa I Clay-Gilmour; Gail L Jones; Helen J Marr; Graham H Jackson; Tobias Menne; Mathew Collin; Adam Ivey; Robert K Hills; Alan K Burnett; Nigel H Russell; Jude Fitzgibbon; Richard A Larson; Michelle M Le Beau; Wendy Stock; Olaf Heidenreich; Abrar Alharbi; David J Allsup; Richard S Houlston; Jean Norden; Anne M Dickinson; Elisabeth Douglas; Clare Lendrem; Ann K Daly; Louise Palm; Kim Piechocki; Sally Jeffries; Martin Bornhäuser; Christoph Röllig; Heidi Altmann; Leo Ruhnke; Desiree Kunadt; Lisa Wagenführ; Heather J Cordell; Rebecca Darlay; Mette K Andersen; Genome-wide acute myeloid leukemia study group

doi:10.1038/s41467-021-26551-x

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Wei-Yu Lin, Sarah E Fordham, Eric Hungate, Nicola J Sunter, Claire Elstob, Yaobo Xu, Catherine Park, Anne Quante, Konstantin Strauch, Christian Gieger, Andrew Skol, Thahira Rahman, Lara Sucheston-Campbell, Junke Wang, Theresa Hahn, Alyssa I Clay-Gilmour, Gail L Jones, Helen J Marr, Graham H Jackson, Tobias MenneMathew Collin, Adam Ivey, Robert K Hills, Alan K Burnett, Nigel H Russell, Jude Fitzgibbon, Richard A Larson, Michelle M Le Beau, Wendy Stock, Olaf Heidenreich, Abrar Alharbi, David J Allsup, Richard S Houlston, Jean Norden, Anne M Dickinson, Elisabeth Douglas, Clare Lendrem, Ann K Daly, Louise Palm, Kim Piechocki, Sally Jeffries, Martin Bornhäuser, Christoph Röllig, Heidi Altmann, Leo Ruhnke, Desiree Kunadt, Lisa Wagenführ, Heather J Cordell, Rebecca Darlay, Mette K Andersen, Genome-wide acute myeloid leukemia study group

Afdeling for Genetik

Abstract

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).

Originalsprog	Engelsk
Artikelnummer	6233
Tidsskrift	Nature Communications
Vol/bind	12
Udgave nummer	1
Sider (fra-til)	6233
ISSN	2041-1722
DOI	https://doi.org/10.1038/s41467-021-26551-x
Status	Udgivet - 29 okt. 2021

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Lin, W.-Y., Fordham, S. E., Hungate, E., Sunter, N. J., Elstob, C., Xu, Y., Park, C., Quante, A., Strauch, K., Gieger, C., Skol, A., Rahman, T., Sucheston-Campbell, L., Wang, J., Hahn, T., Clay-Gilmour, A. I., Jones, G. L., Marr, H. J., Jackson, G. H., ... Genome-wide acute myeloid leukemia study group (2021). Genome-wide association study identifies susceptibility loci for acute myeloid leukemia. Nature Communications, 12(1), 6233. Artikel 6233. https://doi.org/10.1038/s41467-021-26551-x

Lin, W-Y, Fordham, SE, Hungate, E, Sunter, NJ, Elstob, C, Xu, Y, Park, C, Quante, A, Strauch, K, Gieger, C, Skol, A, Rahman, T, Sucheston-Campbell, L, Wang, J, Hahn, T, Clay-Gilmour, AI, Jones, GL, Marr, HJ, Jackson, GH, Menne, T, Collin, M, Ivey, A, Hills, RK, Burnett, AK, Russell, NH, Fitzgibbon, J, Larson, RA, Le Beau, MM, Stock, W, Heidenreich, O, Alharbi, A, Allsup, DJ, Houlston, RS, Norden, J, Dickinson, AM, Douglas, E, Lendrem, C, Daly, AK, Palm, L, Piechocki, K, Jeffries, S, Bornhäuser, M, Röllig, C, Altmann, H, Ruhnke, L, Kunadt, D, Wagenführ, L, Cordell, HJ, Darlay, R, Andersen, MK & Genome-wide acute myeloid leukemia study group 2021, 'Genome-wide association study identifies susceptibility loci for acute myeloid leukemia', Nature Communications, bind 12, nr. 1, 6233, s. 6233. https://doi.org/10.1038/s41467-021-26551-x

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abstract = "Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).",

keywords = "Aldehyde Reductase/genetics, Case-Control Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, HLA Antigens/genetics, Humans, Leukemia, Myeloid, Acute/genetics, Middle Aged, Polymorphism, Single Nucleotide, Reproducibility of Results, Whites/genetics",

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T1 - Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

AU - Lin, Wei-Yu

AU - Fordham, Sarah E

AU - Hungate, Eric

AU - Sunter, Nicola J

AU - Elstob, Claire

AU - Xu, Yaobo

AU - Park, Catherine

AU - Quante, Anne

AU - Strauch, Konstantin

AU - Gieger, Christian

AU - Skol, Andrew

AU - Rahman, Thahira

AU - Sucheston-Campbell, Lara

AU - Wang, Junke

AU - Hahn, Theresa

AU - Clay-Gilmour, Alyssa I

AU - Jones, Gail L

AU - Marr, Helen J

AU - Jackson, Graham H

AU - Menne, Tobias

AU - Collin, Mathew

AU - Ivey, Adam

AU - Hills, Robert K

AU - Burnett, Alan K

AU - Russell, Nigel H

AU - Fitzgibbon, Jude

AU - Larson, Richard A

AU - Le Beau, Michelle M

AU - Stock, Wendy

AU - Heidenreich, Olaf

AU - Alharbi, Abrar

AU - Allsup, David J

AU - Houlston, Richard S

AU - Norden, Jean

AU - Dickinson, Anne M

AU - Douglas, Elisabeth

AU - Lendrem, Clare

AU - Daly, Ann K

AU - Palm, Louise

AU - Piechocki, Kim

AU - Jeffries, Sally

AU - Bornhäuser, Martin

AU - Röllig, Christoph

AU - Altmann, Heidi

AU - Ruhnke, Leo

AU - Kunadt, Desiree

AU - Wagenführ, Lisa

AU - Cordell, Heather J

AU - Darlay, Rebecca

AU - Andersen, Mette K

AU - Genome-wide acute myeloid leukemia study group

PY - 2021/10/29

Y1 - 2021/10/29

N2 - Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).

AB - Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).

KW - Aldehyde Reductase/genetics

KW - Case-Control Studies

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - HLA Antigens/genetics

KW - Humans

KW - Leukemia, Myeloid, Acute/genetics

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Reproducibility of Results

KW - Whites/genetics

UR - http://www.scopus.com/inward/record.url?scp=85118442520&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-26551-x

DO - 10.1038/s41467-021-26551-x

M3 - Journal article

C2 - 34716350

SN - 2041-1722

VL - 12

SP - 6233

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 6233

ER -

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Abstract

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