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Reassessing the association of MUC5B with survival in idiopathic pulmonary fibrosis.

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posted on 2023-09-04, 15:50 authored by Siyang Cai, Richard J Allen, Louise V Wain, Frank Dudbridge
A variant in the mucin 5B gene (MUC5B) is strongly associated with the risk of idiopathic pulmonary fibrosis. However, the same variant is associated with increased survival time. Previous work suggested that this may be explained by index event bias, with the true effect being to decrease survival. Here, we reassessed this claim using more recent methods and datasets. We found that the statistical assumptions of the previous analysis did not hold, and instead, we applied recent methods of corrected weighted least squares, MR-RAPS and Slope-hunter to both the previous data and an updated consortium meta-analysis. However, these analyses did not yield robust evidence for increased or decreased survival. In simulations of a true effect of decreased survival, we did not observe any realistic scenario in which index event bias led to an observed effect of increased survival. We therefore regard as unsafe the claim that MUC5B has a true effect of decreased survival. Alternative explanations should be sought to explain the observed association with increased survival.

Funding

Medical Research Council

LVW is funded by a GSK / Asthma + Lung UK Chair in Respiratory Research (C17-1)

History

Author affiliation

Department of Population Health Sciences, University of Leicester

Version

  • VoR (Version of Record)

Published in

Annals of human genetics

Volume

87

Issue

5

Pagination

248-253

Publisher

Wiley

issn

0003-4800

eissn

1469-1809

Copyright date

2023

Available date

2023-09-04

Spatial coverage

England

Language

eng

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