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, Pepper, Christopher and others, (2021) Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia. Nature Communications, 12 (a665). pp. 1-8. ISSN 2041-1723

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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 × 10−9) 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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Depositing User: Christopher Pepper
Date Deposited: 15 Jul 2021 09:35
Last Modified: 15 Jul 2021 09:46
URI: http://sro.sussex.ac.uk/id/eprint/100495

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