Lin, Wei-Yu, Fordham, Sarah E, Sunter, Nicola, Elstob, Claire, Rahman, Thahira, Willmore, Elaine, Shepherd, Colin, Strathdee, Gordon, Mainou-Fowler, Tryfonia, Piddock, Rachel et al (show 26 more authors)
(2021)
Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia.
NATURE COMMUNICATIONS, 12 (1).
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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<sup>-9</sup>) and 6p (rs3778076, HR = 1.99, 95% CI = 1.55-2.55; P = 5.08 × 10<sup>-8</sup>), 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Disease Progression, Genetic Predisposition to Disease, Prognosis, Multivariate Analysis, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Aged, Middle Aged, Female, Male, Leukemia, Lymphocytic, Chronic, B-Cell, Genome-Wide Association Study, Kaplan-Meier Estimate |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 08 Jul 2021 08:59 |
| Last Modified: | 18 Jan 2023 21:36 |
| DOI: | 10.1038/s41467-020-20822-9 |
| Open Access URL: | http://doi.org/10.1038/s41467-020-20822-9 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3129257 |
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