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; Maria C Fontana; Giovanni Martinelli; Giovanni Marconi; Miguel A Sanz; José Cervera; Inés Gómez-Seguí; Thomas Cluzeau; Chimène Moreilhon; Sophie Raynaud; Heinz Sill; Maria Teresa Voso; Francesco Lo-Coco; Hervé Dombret; Meyling Cheok; Claude Preudhomme; Rosemary E Gale; David Linch; Julia Gaal-Wesinger; Andras Masszi; Daniel Nowak; Wolf-Karsten Hofmann; Amanda Gilkes; Kimmo Porkka; Jelena D Milosevic Feenstra; Robert Kralovics; David Grimwade; Manja Meggendorfer; Torsten Haferlach; Szilvia Krizsán; Csaba Bödör; Friedrich Stölzel; Kenan Onel; James M Allan

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 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, Maria C Fontana, Giovanni Martinelli, Giovanni Marconi, Miguel A Sanz, José Cervera, Inés Gómez-Seguí, Thomas Cluzeau, Chimène Moreilhon, Sophie Raynaud, Heinz Sill, Maria Teresa Voso, Francesco Lo-Coco, Hervé Dombret, Meyling Cheok, Claude Preudhomme, Rosemary E Gale, David Linch, Julia Gaal-Wesinger, Andras Masszi, Daniel Nowak, Wolf-Karsten Hofmann, Amanda Gilkes, Kimmo Porkka, Jelena D Milosevic Feenstra, Robert Kralovics, David Grimwade, Manja Meggendorfer, Torsten Haferlach, Szilvia Krizsán, Csaba Bödör, Friedrich Stölzel, Kenan Onel, James M Allan

Group Heidenreich

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

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).

Original language	English
Article number	6233
Pages (from-to)	6233
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-26551-x
Publication status	Published - 29 Oct 2021

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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10.1038/s41467-021-26551-x

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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., ... Allan, J. M. (2021). Genome-wide association study identifies susceptibility loci for acute myeloid leukemia. Nature communications, 12(1), 6233. Article 6233. https://doi.org/10.1038/s41467-021-26551-x

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title = "Genome-wide association study identifies susceptibility loci for acute myeloid leukemia",

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",

author = "Wei-Yu Lin and Fordham, \{Sarah E\} and Eric Hungate and Sunter, \{Nicola J\} and Claire Elstob and Yaobo Xu and Catherine Park and Anne Quante and Konstantin Strauch and Christian Gieger and Andrew Skol and Thahira Rahman and Lara Sucheston-Campbell and Junke Wang and Theresa Hahn and Clay-Gilmour, \{Alyssa I\} and Jones, \{Gail L\} and Marr, \{Helen J\} and Jackson, \{Graham H\} and Tobias Menne and Mathew Collin and Adam Ivey and Hills, \{Robert K\} and Burnett, \{Alan K\} and Russell, \{Nigel H\} and Jude Fitzgibbon and Larson, \{Richard A\} and \{Le Beau\}, \{Michelle M\} and Wendy Stock and Olaf Heidenreich and Abrar Alharbi and Allsup, \{David J\} and Houlston, \{Richard S\} and Jean Norden and Dickinson, \{Anne M\} and Elisabeth Douglas and Clare Lendrem and Daly, \{Ann K\} and Louise Palm and Kim Piechocki and Sally Jeffries and Martin Bornh{\"a}user and Christoph R{\"o}llig and Heidi Altmann and Leo Ruhnke and Desiree Kunadt and Lisa Wagenf{\"u}hr and Cordell, \{Heather J\} and Rebecca Darlay and Andersen, \{Mette K\} and Fontana, \{Maria C\} and Giovanni Martinelli and Giovanni Marconi and Sanz, \{Miguel A\} and Jos{\'e} Cervera and In{\'e}s G{\'o}mez-Segu{\'i} and Thomas Cluzeau and Chim{\`e}ne Moreilhon and Sophie Raynaud and Heinz Sill and Voso, \{Maria Teresa\} and Francesco Lo-Coco and Herv{\'e} Dombret and Meyling Cheok and Claude Preudhomme and Gale, \{Rosemary E\} and David Linch and Julia Gaal-Wesinger and Andras Masszi and Daniel Nowak and Wolf-Karsten Hofmann and Amanda Gilkes and Kimmo Porkka and \{Milosevic Feenstra\}, \{Jelena D\} and Robert Kralovics and David Grimwade and Manja Meggendorfer and Torsten Haferlach and Szilvia Krizs{\'a}n and Csaba B{\"o}d{\"o}r and Friedrich St{\"o}lzel and Kenan Onel and Allan, \{James M\}",

note = "{\textcopyright} 2021. The Author(s).",

year = "2021",

month = oct,

day = "29",

doi = "10.1038/s41467-021-26551-x",

language = "English",

volume = "12",

pages = "6233",

journal = "Nature communications",

issn = "2041-1723",

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number = "1",

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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, Fontana, MC, Martinelli, G, Marconi, G, Sanz, MA, Cervera, J, Gómez-Seguí, I, Cluzeau, T, Moreilhon, C, Raynaud, S, Sill, H, Voso, MT, Lo-Coco, F, Dombret, H, Cheok, M, Preudhomme, C, Gale, RE, Linch, D, Gaal-Wesinger, J, Masszi, A, Nowak, D, Hofmann, W-K, Gilkes, A, Porkka, K, Milosevic Feenstra, JD, Kralovics, R, Grimwade, D, Meggendorfer, M, Haferlach, T, Krizsán, S, Bödör, C, Stölzel, F, Onel, K & Allan, JM 2021, 'Genome-wide association study identifies susceptibility loci for acute myeloid leukemia', Nature communications, vol. 12, no. 1, 6233, pp. 6233. https://doi.org/10.1038/s41467-021-26551-x

TY - JOUR

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 - Fontana, Maria C

AU - Martinelli, Giovanni

AU - Marconi, Giovanni

AU - Sanz, Miguel A

AU - Cervera, José

AU - Gómez-Seguí, Inés

AU - Cluzeau, Thomas

AU - Moreilhon, Chimène

AU - Raynaud, Sophie

AU - Sill, Heinz

AU - Voso, Maria Teresa

AU - Lo-Coco, Francesco

AU - Dombret, Hervé

AU - Cheok, Meyling

AU - Preudhomme, Claude

AU - Gale, Rosemary E

AU - Linch, David

AU - Gaal-Wesinger, Julia

AU - Masszi, Andras

AU - Nowak, Daniel

AU - Hofmann, Wolf-Karsten

AU - Gilkes, Amanda

AU - Porkka, Kimmo

AU - Milosevic Feenstra, Jelena D

AU - Kralovics, Robert

AU - Grimwade, David

AU - Meggendorfer, Manja

AU - Haferlach, Torsten

AU - Krizsán, Szilvia

AU - Bödör, Csaba

AU - Stölzel, Friedrich

AU - Onel, Kenan

AU - Allan, James M

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 - https://www.scopus.com/pages/publications/85118442520

U2 - 10.1038/s41467-021-26551-x

DO - 10.1038/s41467-021-26551-x

M3 - Article

C2 - 34716350

SN - 2041-1723

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

Keywords

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