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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Lin WY,Fordham SE,Sunter N,Elstob C,Rahman T,Willmore E,Shepherd C,Strathdee G,Mainou-Fowler T,Piddock R,Mearns H,Barrow T,Houlston RS,Marr H,Wallis J,Summerfield G,Marshall S,Pettitt A,Pepper C,Fegan C,Forconi F

doi

10.1038/s41467-020-20822-9

subject

Has Abstract

pub_date

2021-01-28 00:00:00

pages

665

issue

1

issn

2041-1723

pii

10.1038/s41467-020-20822-9

journal_volume

12

pub_type

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