Imperial College London
Alternate

Professor Toby Maher

Faculty of Medicine, National Heart & Lung Institute

Professor of Interstitial Lung Disease
 
 
 
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Contact

 

+44 (0)20 7594 2151t.maher

 
 
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Assistant

 

Ms Georgina Moss +44 (0)20 7594 2151

 
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Location

 

364Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Allen:2023:10.1016/S2213-2600(22)00251-X,
author = {Allen, RJ and Oldham, JM and Jenkins, DA and Leavy, OC and Guillen-Guio, B and Melbourne, CA and Ma, S-F and Jou, J and Kim, JS and CleanUP-IPF, Investigators of the Pulmonary Trials Cooperative and Fahy, WA and Oballa, E and Hubbard, RB and Navaratnam, V and Braybrooke, R and Saini, G and Roach, KM and Tobin, MD and Hirani, N and Whyte, MKB and Kaminski, N and Zhang, Y and Martinez, FJ and Linderholm, AL and Adegunsoye, A and Strek, ME and Maher, TM and Molyneaux, PL and Flores, C and Noth, I and Gisli, Jenkins R and Wain, LV},
doi = {10.1016/S2213-2600(22)00251-X},
journal = {The Lancet Respiratory Medicine},
pages = {65--73},
title = {Longitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: a genome-wide association study},
url = {http://dx.doi.org/10.1016/S2213-2600(22)00251-X},
volume = {11},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an incurable lung disease characterised by progressive scarring leading to alveolar stiffness, reduced lung capacity, and impeded gas transfer. We aimed to identify genetic variants associated with declining lung capacity or declining gas transfer after diagnosis of IPF. METHODS: We did a genome-wide meta-analysis of longitudinal measures of forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) in individuals diagnosed with IPF. Individuals were recruited to three studies between June, 1996, and August, 2017, from across centres in the US, UK, and Spain. Suggestively significant variants were investigated further in an additional independent study (CleanUP-IPF). All four studies diagnosed cases following American Thoracic Society/European Respiratory Society guidelines. Variants were defined as significantly associated if they had a meta-analysis p<5 × 10-8 when meta-analysing across all discovery and follow-up studies, had consistent direction of effects across all four studies, and were nominally significant (p<0·05) in each study. FINDINGS: 1329 individuals with a total of 5216 measures were included in the FVC analysis. 975 individuals with a total of 3361 measures were included in the DLCO analysis. For the discovery genome-wide analyses, 7 611 174 genetic variants were included in the FVC analysis and 7 536 843 in the DLCO analysis. One variant (rs115982800) located in an antisense RNA gene for protein kinase N2 (PKN2) showed a genome-wide significant association with FVC decline (-140 mL/year per risk allele [95% CI -180 to -100]; p=9·14 × 10-12). INTERPRETATION: Our analysis identifies a genetic variant associated with disease progression, which might highlight a new biological mechanism for IPF. We found that PKN2, a Rho and Rac effector protein, is the most likely gene of interest fro
AU  - Allen,RJ
AU  - Oldham,JM
AU  - Jenkins,DA
AU  - Leavy,OC
AU  - Guillen-Guio,B
AU  - Melbourne,CA
AU  - Ma,S-F
AU  - Jou,J
AU  - Kim,JS
AU  - CleanUP-IPF,Investigators of the Pulmonary Trials Cooperative
AU  - Fahy,WA
AU  - Oballa,E
AU  - Hubbard,RB
AU  - Navaratnam,V
AU  - Braybrooke,R
AU  - Saini,G
AU  - Roach,KM
AU  - Tobin,MD
AU  - Hirani,N
AU  - Whyte,MKB
AU  - Kaminski,N
AU  - Zhang,Y
AU  - Martinez,FJ
AU  - Linderholm,AL
AU  - Adegunsoye,A
AU  - Strek,ME
AU  - Maher,TM
AU  - Molyneaux,PL
AU  - Flores,C
AU  - Noth,I
AU  - Gisli,Jenkins R
AU  - Wain,LV
DO  - 10.1016/S2213-2600(22)00251-X
EP  - 73
PY  - 2023///
SN  - 2213-2600
SP  - 65
TI  - Longitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: a genome-wide association study
T2  - The Lancet Respiratory Medicine
UR  - http://dx.doi.org/10.1016/S2213-2600(22)00251-X
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35985358
UR  - https://www.sciencedirect.com/science/article/pii/S221326002200251X?via%3Dihub
UR  - http://hdl.handle.net/10044/1/99299
VL  - 11
ER  -
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