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{Hobbs:2019:10.1164/rccm.201903-0511OC,
author = {Hobbs, BD and Putman, RK and Araki, T and Nishino, M and Gudmundsson, G and Gudnason, V and Eiriksdottir, G and Zilhao, Nogueira NR and Dupuis, J and Xu, H and O'Connor, GT and Manichaikul, A and Nguyen, J and Podolanczuk, AJ and Madahar, P and Rotter, JI and Lederer, DJ and Barr, RG and Rich, SS and Ampleford, EJ and Ortega, VE and Peters, SP and O'Neal, WK and Newell, JD and Bleecker, ER and Meyers, DA and Allen, RJ and Oldham, JM and Ma, S-F and Noth, I and Jenkins, RG and Maher, TM and Hubbard, RB and Wain, LV and Fingerlin, TE and Schwartz, DA and Washko, GR and Rosas, IO and Silverman, EK and Hatabu, H and Cho, MH and Hunninghake, GM and COPDGene, Investigators and ECLIPSE, Investigators and SPIROMICS, Research Group and and, UK ILD Consortium},
doi = {10.1164/rccm.201903-0511OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {1402--1413},
title = {Overlap of genetic risk between interstitial lung abnormalities and idiopathic pulmonary fibrosis.},
url = {http://dx.doi.org/10.1164/rccm.201903-0511OC},
volume = {200},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Rationale Interstitial lung abnormalities (ILA) are associated with the highest genetic risk locus for IPF; however, the extent to which there is additional overlap with IPF, or unique associations among those with ILA is not known. Objectives To perform a genome-wide association study (GWAS) of ILA. Methods: ILA and the subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES, COPDGene, Framingham Heart, ECLIPSE, MESA, and SPIROMICS studies. We performed a GWAS of ILA in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF. Measurements and Main Results Genome-wide genotyping data were available in 1,699 ILA cases and 10,274 controls. The MUC5B promoter variant rs35705950 was significantly associated with both ILA (p=2.6x10-27) and subpleural ILA (p=1.6x10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, p=3.8x10-8) and FCF1P3 (rs73199442, p=4.8x10-8) with ILA, and HTRE1 (rs7744971, p=4.2x10-8) with subpleural-predominant ILA. These novel associations were not associated with IPF. Of 12 previously reported IPF GWAS loci, 5 (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (p<0.05/12) with ILA. Conclusions In a GWAS of ILA in six studies, we confirmed the association with a MUC5B promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common and suggest distinct genetically-driven biologic pathways between ILA and IPF.
AU  - Hobbs,BD
AU  - Putman,RK
AU  - Araki,T
AU  - Nishino,M
AU  - Gudmundsson,G
AU  - Gudnason,V
AU  - Eiriksdottir,G
AU  - Zilhao,Nogueira NR
AU  - Dupuis,J
AU  - Xu,H
AU  - O'Connor,GT
AU  - Manichaikul,A
AU  - Nguyen,J
AU  - Podolanczuk,AJ
AU  - Madahar,P
AU  - Rotter,JI
AU  - Lederer,DJ
AU  - Barr,RG
AU  - Rich,SS
AU  - Ampleford,EJ
AU  - Ortega,VE
AU  - Peters,SP
AU  - O'Neal,WK
AU  - Newell,JD
AU  - Bleecker,ER
AU  - Meyers,DA
AU  - Allen,RJ
AU  - Oldham,JM
AU  - Ma,S-F
AU  - Noth,I
AU  - Jenkins,RG
AU  - Maher,TM
AU  - Hubbard,RB
AU  - Wain,LV
AU  - Fingerlin,TE
AU  - Schwartz,DA
AU  - Washko,GR
AU  - Rosas,IO
AU  - Silverman,EK
AU  - Hatabu,H
AU  - Cho,MH
AU  - Hunninghake,GM
AU  - COPDGene,Investigators
AU  - ECLIPSE,Investigators
AU  - SPIROMICS,Research Group
AU  - and,UK ILD Consortium
DO  - 10.1164/rccm.201903-0511OC
EP  - 1413
PY  - 2019///
SN  - 1073-449X
SP  - 1402
TI  - Overlap of genetic risk between interstitial lung abnormalities and idiopathic pulmonary fibrosis.
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - http://dx.doi.org/10.1164/rccm.201903-0511OC
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31339356
UR  - https://www.atsjournals.org/doi/10.1164/rccm.201903-0511OC
UR  - http://hdl.handle.net/10044/1/72042
VL  - 200
ER  -
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