Imperial College London
Portrait Picture

ProfessorPhilipMolyneaux

Faculty of Medicine, National Heart & Lung Institute

Professor of Interstitial Lung Disease
 
 
 
//

Contact

 

p.molyneaux

 
 
//

Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Peljto:2023:10.1164/rccm.202207-1331oc,
author = {Peljto, AL and Blumhagen, RZ and Walts, AD and Cardwell, J and Powers, J and Corte, TJ and Dickinson, JL and Glaspole, I and Moodley, YP and Vasakova, MK and Bendstrup, E and Davidsen, JR and Borie, R and Crestani, B and Dieude, P and Bonella, F and Costabel, U and Gudmundsson, G and Donnelly, SC and Egan, J and Henry, MT and Keane, MP and Kennedy, MP and McCarthy, C and McElroy, AN and Olaniyi, JA and O'Reilly, KMA and Richeldi, L and Leone, PM and Poletti, V and Puppo, F and Tomassetti, S and Luzzi, V and Kokturk, N and Mogulkoc, N and Fiddler, CA and Hirani, N and Jenkins, G and Maher, TM and Molyneaux, PL and Parfrey, H and Braybrooke, R and Blackwell, TS and Jackson, PD and Nathan, SD and Porteous, MK and Brown, KK and Christie, JD and Collard, HR and Eickelberg, O and Foster, EE and Gibson, KF and Glassberg, M and Kass, D and Kropski, JA and Lederer, D and Linderholm, AL and Loyd, J and Mathai, SK and Montesi, SB and Noth, I and Oldham, JM and Palmisciano, AJ and Reichner, CA and},
doi = {10.1164/rccm.202207-1331oc},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {1194--1202},
title = {Idiopathic pulmonary fibrosis is associated with common genetic variants and limited rare variants},
url = {http://dx.doi.org/10.1164/rccm.202207-1331oc},
volume = {207},
year = {2023}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Rationale: Idiopathic pulmonary fibrosis is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to non-genetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants genome-wide may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ≤0.01) within genes or regions. We also identified individual variants that are influential within genes and estimated the heritability of IPF based on rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP-heritability of IPF was estimated to be 32% (s.e. 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.
AU  - Peljto,AL
AU  - Blumhagen,RZ
AU  - Walts,AD
AU  - Cardwell,J
AU  - Powers,J
AU  - Corte,TJ
AU  - Dickinson,JL
AU  - Glaspole,I
AU  - Moodley,YP
AU  - Vasakova,MK
AU  - Bendstrup,E
AU  - Davidsen,JR
AU  - Borie,R
AU  - Crestani,B
AU  - Dieude,P
AU  - Bonella,F
AU  - Costabel,U
AU  - Gudmundsson,G
AU  - Donnelly,SC
AU  - Egan,J
AU  - Henry,MT
AU  - Keane,MP
AU  - Kennedy,MP
AU  - McCarthy,C
AU  - McElroy,AN
AU  - Olaniyi,JA
AU  - O'Reilly,KMA
AU  - Richeldi,L
AU  - Leone,PM
AU  - Poletti,V
AU  - Puppo,F
AU  - Tomassetti,S
AU  - Luzzi,V
AU  - Kokturk,N
AU  - Mogulkoc,N
AU  - Fiddler,CA
AU  - Hirani,N
AU  - Jenkins,G
AU  - Maher,TM
AU  - Molyneaux,PL
AU  - Parfrey,H
AU  - Braybrooke,R
AU  - Blackwell,TS
AU  - Jackson,PD
AU  - Nathan,SD
AU  - Porteous,MK
AU  - Brown,KK
AU  - Christie,JD
AU  - Collard,HR
AU  - Eickelberg,O
AU  - Foster,EE
AU  - Gibson,KF
AU  - Glassberg,M
AU  - Kass,D
AU  - Kropski,JA
AU  - Lederer,D
AU  - Linderholm,AL
AU  - Loyd,J
AU  - Mathai,SK
AU  - Montesi,SB
AU  - Noth,I
AU  - Oldham,JM
AU  - Palmisciano,AJ
AU  - Reichner,CA
AU  - Rojas,M
AU  - Roman,J
AU  - Schluger,N
AU  - Shea,BS
AU  - Swigris,JJ
AU  - Wolters,PJ
AU  - Zhang,Y
AU  - Prele,CMA
AU  - Enghelmayer,JI
AU  - Otaola,M
AU  - Ryerson,CJ
AU  - Salinas,M
AU  - Sterclova,M
AU  - Gebremariam,TH
AU  - Myllärniemi,M
AU  - Carbone,R
AU  - Furusawa,H
AU  - Hirose,M
AU  - Inoue,Y
AU  - Miyazaki,Y
AU  - Ohta,K
AU  - Ohta,S
AU  - Okamoto,T
AU  - Kim,DS
AU  - Pardo,A
AU  - Selman,M
AU  - Aranda,AU
AU  - Park,MS
AU  - Park,JS
AU  - Song,JW
AU  - Molina-Molina,M
AU  - Planas-Cerezales,L
AU  - Westergren-Thorsson,G
AU  - Smith,AV
AU  - Manichaikul,AW
AU  - Kim,JS
AU  - Rich,SS
AU  - Oelsner,EC
AU  - Barr,RG
AU  - Rotter,JI
AU  - Dupuis,J
AU  - O'Connor,G
AU  - Vasan,RS
AU  - Cho,MH
AU  - Silverman,EK
AU  - Schwarz,MI
AU  - Steele,MP
AU  - Lee,JS
AU  - Yang,IV
AU  - Fingerlin,TE
AU  - Schwartz,DA
DO  - 10.1164/rccm.202207-1331oc
EP  - 1202
PY  - 2023///
SN  - 1073-449X
SP  - 1194
TI  - Idiopathic pulmonary fibrosis is associated with common genetic variants and limited rare variants
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - http://dx.doi.org/10.1164/rccm.202207-1331oc
UR  - https://www.atsjournals.org/doi/10.1164/rccm.202207-1331OC
UR  - http://hdl.handle.net/10044/1/101620
VL  - 207
ER  -
Download