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Preliminary Results from Genome-wide Meta-analysis of Survival Time in Idiopathic Pulmonary Fibrosis

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conference contribution
posted on 18.05.2020, 15:52 by RJ Allen, J Oldham, JML Salazar, SF Ma, R Braybrooke, I Sayers, IP Hall, MD Tobin, I Noth, RG Jenkins, C Flores, LV Wain

Introduction: Idiopathic pulmonary fibrosis (IPF) is a rare lung disease of unknown cause, with few effective treatments available and poor prognosis (median survival time of 3 years). Genome-wide studies have identified variants associated with susceptibility to IPF. Although the effects of those variants on survival time have been investigated, no study has investigated survival time genome-wide for IPF. We set out to identify novel signals of association with IPF survival time and to replicate previous reports that variants in MUC5B that are associated with increased susceptibility to IPF, are paradoxically associated with an increase in survival time.

Methods: We performed genome-wide analyses investigating survival time in a UK IPF study and a USA IPF study and meta-analysed the results. Survival analyses were performed on variants with minor allele frequency (MAF)>0.5% in both studies using a Cox Proportional Hazards model. Independent variants meeting meta-analysis P<5×10−6 and P<0.05 in each of the separate studies (with consistent direction of effect estimate between studies), are being investigated further in an independent replication dataset.

Results: A total of 963 individuals and 7,730,466 variants were included in the final meta-analysis with maximum follow-up of 16.5 years. A total of 79 independent signals (11 with MAF>5%) reached the criteria described above. Consistent with previous reports, the allele in rs35705950 in MUC5B that is associated with increased susceptibility to IPF, shows some association with increased survival time (HR=0.73, 95% CI: [0.61, 0.87], P=5.08×10−4).

Conclusions: This details the first analysis to investigate survival time genome-wide in IPF.

History

Citation

GENETIC EPIDEMIOLOGY, 2017, 41 (7), pp. 669-670 (2)

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health Sciences

Source

Annual Meeting of the International-Genetic-Epidemiology-Society (IGES), Queens Coll, Cambridge, ENGLAND

Version

AM (Accepted Manuscript)

Published in

GENETIC EPIDEMIOLOGY

Volume

41

Issue

7

Pagination

669-670 (2)

Publisher

WILEY

issn

0741-0395

eissn

1098-2272

Copyright date

2017

Available date

21/08/2017

Publisher version

https://onlinelibrary.wiley.com/doi/10.1002/gepi.22062

Notes

Abstract only

Spatial coverage

Queens College, Cambridge, ENGLAND

Temporal coverage: start date

09/09/2017

Temporal coverage: end date

11/09/2017

Language

en