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{Fingerlin:2016:10.1186/s12863-016-0377-2,
author = {Fingerlin, TE and Zhang, W and Yang, IV and Ainsworth, HC and Russell, PH and Blumhagen, RZ and Schwarz, MI and Brown, KK and Steele, MP and Loyd, JE and Cosgrove, GP and Lynch, DA and Groshong, S and Collard, HR and Wolters, PJ and Bradford, WZ and Kossen, K and Seiwert, SD and du, Bois RM and Garcia, CK and Devine, MS and Gudmundsson, G and Isaksson, HJ and Kaminski, N and Zhang, Y and Gibson, KF and Lancaster, LH and Maher, TM and Molyneaux, PL and Wells, AU and Moffatt, MF and Selman, M and Pardo, A and Kim, DS and Crapo, JD and Make, BJ and Regan, EA and Walek, DS and Daniel, JJ and Kamatani, Y and Zelenika, D and Murphy, E and Smith, K and McKean, D and Pedersen, BS and Talbert, J and Powers, J and Markin, CR and Beckman, KB and Lathrop, M and Freed, B and Langefeld, CD and Schwartz, DA},
doi = {10.1186/s12863-016-0377-2},
journal = {BMC Genetics},
title = {Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia},
url = {http://dx.doi.org/10.1186/s12863-016-0377-2},
volume = {17},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Fibrotic idiopathic interstitial pneumonias (fIIP) are a group of fatal lung diseases with largely unknown etiology and without definitive treatment other than lung transplant to prolong life. There is strong evidence for the importance of both rare and common genetic risk alleles in familial and sporadic disease. We have previously used genome-wide single nucleotide polymorphism data to identify 10 risk loci for fIIP. Here we extend that work to imputed genome-wide genotypes and conduct new RNA sequencing studies of lung tissue to identify and characterize new fIIP risk loci. RESULTS: We performed genome-wide genotype imputation association analyses in 1616 non-Hispanic white (NHW) cases and 4683 NHW controls followed by validation and replication (878 cases, 2017 controls) genotyping and targeted gene expression in lung tissue. Following meta-analysis of the discovery and replication populations, we identified a novel fIIP locus in the HLA region of chromosome 6 (rs7887 P meta  = 3.7 × 10(-09)). Imputation of classic HLA alleles identified two in high linkage disequilibrium that are associated with fIIP (DRB115:01 P = 1.3 × 10(-7) and DQB106:02 P = 6.1 × 10(-8)). Targeted RNA-sequencing of the HLA locus identified 21 genes differentially expressed between fibrotic and control lung tissue (Q < 0.001), many of which are involved in immune and inflammatory response regulation. In addition, the putative risk alleles, DRB115:01 and DQB106:02, are associated with expression of the DQB1 gene among fIIP cases (Q < 1 × 10(-16)). CONCLUSIONS: We have identified a genome-wide significant association between the HLA region and fIIP. Two HLA alleles are associated with fIIP and affect expression of HLA genes in lung tissue, indicating that the potential genetic risk due to HLA alleles may involve gene regula
AU  - Fingerlin,TE
AU  - Zhang,W
AU  - Yang,IV
AU  - Ainsworth,HC
AU  - Russell,PH
AU  - Blumhagen,RZ
AU  - Schwarz,MI
AU  - Brown,KK
AU  - Steele,MP
AU  - Loyd,JE
AU  - Cosgrove,GP
AU  - Lynch,DA
AU  - Groshong,S
AU  - Collard,HR
AU  - Wolters,PJ
AU  - Bradford,WZ
AU  - Kossen,K
AU  - Seiwert,SD
AU  - du,Bois RM
AU  - Garcia,CK
AU  - Devine,MS
AU  - Gudmundsson,G
AU  - Isaksson,HJ
AU  - Kaminski,N
AU  - Zhang,Y
AU  - Gibson,KF
AU  - Lancaster,LH
AU  - Maher,TM
AU  - Molyneaux,PL
AU  - Wells,AU
AU  - Moffatt,MF
AU  - Selman,M
AU  - Pardo,A
AU  - Kim,DS
AU  - Crapo,JD
AU  - Make,BJ
AU  - Regan,EA
AU  - Walek,DS
AU  - Daniel,JJ
AU  - Kamatani,Y
AU  - Zelenika,D
AU  - Murphy,E
AU  - Smith,K
AU  - McKean,D
AU  - Pedersen,BS
AU  - Talbert,J
AU  - Powers,J
AU  - Markin,CR
AU  - Beckman,KB
AU  - Lathrop,M
AU  - Freed,B
AU  - Langefeld,CD
AU  - Schwartz,DA
DO  - 10.1186/s12863-016-0377-2
PY  - 2016///
SN  - 1471-2156
TI  - Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia
T2  - BMC Genetics
UR  - http://dx.doi.org/10.1186/s12863-016-0377-2
UR  - http://hdl.handle.net/10044/1/33900
VL  - 17
ER  -
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