Imperial College London
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ProfessorPhilipMolyneaux

Faculty of Medicine, National Heart & Lung Institute

Professor of Interstitial Lung Disease
 
 
 
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p.molyneaux

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Allen:2017:10.1016/S2213-2600(17)30387-9,
author = {Allen, RJ and Porte, J and Braybrooke, R and Flores, C and Fingerlin, TE and Oldham, JM and Guillen-Guio, B and Ma, S-F and Okamoto, T and John, AE and Obeidat, M and Yang, IV and Henry, A and Hubbard, RB and Navaratnam, V and Saini, G and Thompson, N and Booth, HL and Hart, SP and Hill, MR and Hirani, N and Maher, TM and McAnulty, RJ and Millar, AB and Molyneaux, PL and Parfrey, H and Rassl, DM and Whyte, MKB and Fahy, WA and Marshall, RP and Oballa, E and Bossé, Y and Nickle, DC and Sin, DD and Timens, W and Shrine, N and Sayers, I and Hall, IP and Noth, I and Schwartz, DA and Tobin, MD and Wain, LV and Jenkins, RG},
doi = {10.1016/S2213-2600(17)30387-9},
journal = {Lancet Respiratory Medicine},
pages = {869--880},
title = {Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study.},
url = {http://dx.doi.org/10.1016/S2213-2600(17)30387-9},
volume = {5},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high mortality, uncertain cause, and few treatment options. Studies have identified a significant genetic risk associated with the development of IPF; however, mechanisms by which genetic risk factors promote IPF remain unclear. We aimed to identify genetic variants associated with IPF susceptibility and provide mechanistic insight using gene and protein expression analyses. METHODS: We used a two-stage approach: a genome-wide association study in patients with IPF of European ancestry recruited from nine different centres in the UK and controls selected from UK Biobank (stage 1) matched for age, sex, and smoking status; and a follow-up of associated genetic variants in independent datasets of patients with IPF and controls from two independent US samples from the Chicago consortium and the Colorado consortium (stage 2). We investigated the effect of novel signals on gene expression in large transcriptomic and genomic data resources, and examined expression using lung tissue samples from patients with IPF and controls. FINDINGS: 602 patients with IPF and 3366 controls were selected for stage 1. For stage 2, 2158 patients with IPF and 5195 controls were selected. We identified a novel genome-wide significant signal of association with IPF susceptibility near A-kinase anchoring protein 13 (AKAP13; rs62025270, odds ratio [OR] 1·27 [95% CI 1·18-1·37], p=1·32×10(-9)) and confirmed previously reported signals, including in mucin 5B (MUC5B; rs35705950, OR 2·89 [2·56-3·26], p=1·12×10(-66)) and desmoplakin (DSP; rs2076295, OR 1·44 [1·35-1·54], p=7·81×10(-28)). For rs62025270, the allele A associated with increased susceptibility to IPF was also associated with increased expression of AKAP13 mRNA in lung tissue from patients who had lung resection procedures (n=1111). We showed th
AU  - Allen,RJ
AU  - Porte,J
AU  - Braybrooke,R
AU  - Flores,C
AU  - Fingerlin,TE
AU  - Oldham,JM
AU  - Guillen-Guio,B
AU  - Ma,S-F
AU  - Okamoto,T
AU  - John,AE
AU  - Obeidat,M
AU  - Yang,IV
AU  - Henry,A
AU  - Hubbard,RB
AU  - Navaratnam,V
AU  - Saini,G
AU  - Thompson,N
AU  - Booth,HL
AU  - Hart,SP
AU  - Hill,MR
AU  - Hirani,N
AU  - Maher,TM
AU  - McAnulty,RJ
AU  - Millar,AB
AU  - Molyneaux,PL
AU  - Parfrey,H
AU  - Rassl,DM
AU  - Whyte,MKB
AU  - Fahy,WA
AU  - Marshall,RP
AU  - Oballa,E
AU  - Bossé,Y
AU  - Nickle,DC
AU  - Sin,DD
AU  - Timens,W
AU  - Shrine,N
AU  - Sayers,I
AU  - Hall,IP
AU  - Noth,I
AU  - Schwartz,DA
AU  - Tobin,MD
AU  - Wain,LV
AU  - Jenkins,RG
DO  - 10.1016/S2213-2600(17)30387-9
EP  - 880
PY  - 2017///
SN  - 2213-2600
SP  - 869
TI  - Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study.
T2  - Lancet Respiratory Medicine
UR  - http://dx.doi.org/10.1016/S2213-2600(17)30387-9
UR  - http://hdl.handle.net/10044/1/52649
VL  - 5
ER  -
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