41467_2020_Article_20822.pdf (1.94 MB)
Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia
journal contribution
posted on 2023-06-10, 00:22 authored by Wei-Yu Lin, Sarah E Fordham, Nicola Sunter, Claire Elstob, Thahira Rahman, Elaine Willmore, Colin Shepherd, Gordon Strathdee, Tryfonia Mainou-Fowler, Rachel Piddock, Hannah Mearns, Timothy Barrow, Richard S Houlston, Helen Marr, Christopher PepperChristopher Pepper, othersPrognostication 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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- Published
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- Published version
Journal
Nature CommunicationsISSN
2041-1723Publisher
Nature ResearchExternal DOI
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a665Volume
12Page range
1-8Department affiliated with
- BSMS Publications
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- Yes
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- Yes
Legacy Posted Date
2021-07-15First Open Access (FOA) Date
2021-07-15First Compliant Deposit (FCD) Date
2021-07-14Usage metrics
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