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Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia

Lin, Wei-Yu, Fordham, Sarah E., Sunter, Nicola, Elstob, Claire, Rahman, Thahira, Willmore, Elaine, Shepherd, Colin, Strathdee, Gordon, Mainou-Fowler, Tryfonia, Piddock, Rachel, Mearns, Hannah, Barrow, Timothy, Houlston, Richard S., Marr, Helen, Wallis, Jonathan P, Summerfield, Geoffrey, Marshall, Scott, Pettitt, Andrew, Pepper, Christopher, Fegan, Christopher, Forconi, Francesco, Dyer, Martin J. S., Jayne, Sandrine, Sellors, April, Schuh, Anna, Robbe, Pauline, Oscier, David, Bailey, James, Rais, Syed, Bentley, Alison, Cawkwell, Lynn, Evans, Paul, Hillmen, Peter, Pratt, Guy, Allsup, David J. and Allan, James M. (2021) Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia. Nature Communications, 12 (1). p. 665. ISSN 2041-1723

Item Type: Article

Abstract

Abstract: Prognostication in patients with chronic lymphocytic leukemia (CLL) is challenging due to heterogeneity in clinical course. We hypothesize that constitutional genetic variation affects disease progression and could aid prognostication. Pooling data from seven studies incorporating 842 cases identifies two genomic locations associated with time from diagnosis to treatment, including 10q26.13 (rs736456, hazard ratio (HR) = 1.78, 95% confidence interval (CI) = 1.47–2.15; P = 2.71 × 10−9) and 6p (rs3778076, HR = 1.99, 95% CI = 1.55–2.55; P = 5.08 × 10−8), which are particularly powerful prognostic markers in patients with early stage CLL otherwise characterized by low-risk features. Expression quantitative trait loci analysis identifies putative functional genes implicated in modulating B-cell receptor or innate immune responses, key pathways in CLL pathogenesis. In this work we identify rs736456 and rs3778076 as prognostic in CLL, demonstrating that disease progression is determined by constitutional genetic variation as well as known somatic drivers.

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Additional Information: ** From Springer Nature via Jisc Publications Router ** History: received 10-10-2019; accepted 16-12-2020; registration 23-12-2020; online 28-01-2021; pub-electronic 28-01-2021; collection 12-2021. ** Licence for this article: http://creativecommons.org/licenses/by/4.0/
Uncontrolled Keywords: Article, /631/67/68, /631/67/69, /631/67/1990/283/1895, /631/208/721, /692/53/2422, /45, /45/43, article
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Identifiers

Item ID: 13111
Identification Number: https://doi.org/10.1038/s41467-020-20822-9
ISSN: 2041-1723
URI: http://sure.sunderland.ac.uk/id/eprint/13111
Official URL: https://www.nature.com/articles/s41467-020-20822-9...

Users with ORCIDS

ORCID for Wei-Yu Lin: ORCID iD orcid.org/0000-0002-9267-7988
ORCID for Claire Elstob: ORCID iD orcid.org/0000-0003-4252-493X
ORCID for Gordon Strathdee: ORCID iD orcid.org/0000-0001-9681-8429
ORCID for Hannah Mearns: ORCID iD orcid.org/0000-0002-8581-1288
ORCID for Timothy Barrow: ORCID iD orcid.org/0000-0003-4551-3857
ORCID for Richard S. Houlston: ORCID iD orcid.org/0000-0002-5268-0242
ORCID for Scott Marshall: ORCID iD orcid.org/0000-0001-8574-7012
ORCID for Christopher Pepper: ORCID iD orcid.org/0000-0003-3603-8839
ORCID for Francesco Forconi: ORCID iD orcid.org/0000-0002-2211-1831
ORCID for Martin J. S. Dyer: ORCID iD orcid.org/0000-0002-5033-2236
ORCID for Anna Schuh: ORCID iD orcid.org/0000-0002-3938-8490
ORCID for James Bailey: ORCID iD orcid.org/0000-0001-8540-8627
ORCID for David J. Allsup: ORCID iD orcid.org/0000-0001-6159-6109
ORCID for James M. Allan: ORCID iD orcid.org/0000-0002-7580-5087

Catalogue record

Date Deposited: 02 Feb 2021 11:43
Last Modified: 02 Feb 2021 11:45

Contributors

Author: Wei-Yu Lin ORCID iD
Author: Claire Elstob ORCID iD
Author: Gordon Strathdee ORCID iD
Author: Hannah Mearns ORCID iD
Author: Timothy Barrow ORCID iD
Author: Richard S. Houlston ORCID iD
Author: Scott Marshall ORCID iD
Author: Christopher Pepper ORCID iD
Author: Francesco Forconi ORCID iD
Author: Martin J. S. Dyer ORCID iD
Author: Anna Schuh ORCID iD
Author: James Bailey ORCID iD
Author: David J. Allsup ORCID iD
Author: James M. Allan ORCID iD
Author: Sarah E. Fordham
Author: Nicola Sunter
Author: Thahira Rahman
Author: Elaine Willmore
Author: Colin Shepherd
Author: Tryfonia Mainou-Fowler
Author: Rachel Piddock
Author: Helen Marr
Author: Jonathan P Wallis
Author: Geoffrey Summerfield
Author: Andrew Pettitt
Author: Christopher Fegan
Author: Sandrine Jayne
Author: April Sellors
Author: Pauline Robbe
Author: David Oscier
Author: Syed Rais
Author: Alison Bentley
Author: Lynn Cawkwell
Author: Paul Evans
Author: Peter Hillmen
Author: Guy Pratt

University Divisions

Faculty of Health Sciences and Wellbeing > School of Nursing and Health Sciences

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