Imperial College London
Alternate

ProfessorJohnChambers

Faculty of Medicine, School of Public Health

Professor of Cardiovascular Medicine & Epidemiology
 
 
 
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Contact

 

+44 (0)7866 365 776john.chambers

 
 
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Location

 

172Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wain:2015:10.1016/S2213-2600(15)00283-0,
author = {Wain, LV and Shrine, N and Miller, S and Jackson, VE and Ntalla, I and Artigas, MS and Billington, CK and Kheirallah, AK and Allen, R and Cook, JP and Probert, K and Obeidat, M and Bosse, Y and Hao, K and Postma, DS and Pare, PD and Ramasamy, A and Maegi, R and Mihailov, E and Reinmaa, E and Melen, E and O'Connell, J and Frangou, E and Delaneau, O and Freeman, C and Petkova, D and McCarthy, M and Sayers, I and Deloukas, P and Hubbard, R and Pavord, I and Hansell, AL and Thomson, NC and Zeggini, E and Morris, AP and Marchini, J and Strachan, DP and Tobin, MD and Hall, IP},
doi = {10.1016/S2213-2600(15)00283-0},
journal = {Lancet Respiratory Medicine},
pages = {769--781},
title = {Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank},
url = {http://dx.doi.org/10.1016/S2213-2600(15)00283-0},
volume = {3},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundUnderstanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD). We used UK Biobank data to study the genetic causes of smoking behaviour and lung health.MethodsWe sampled individuals of European ancestry from UK Biobank, from the middle and extremes of the forced expiratory volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and never smokers. We developed a custom array for UK Biobank to provide optimum genome-wide coverage of common and low-frequency variants, dense coverage of genomic regions already implicated in lung health and disease, and to assay rare coding variants relevant to the UK population. We investigated whether there were shared genetic causes between different phenotypes defined by extremes of FEV1. We also looked for novel variants associated with extremes of FEV1 and smoking behaviour and assessed regions of the genome that had already shown evidence for a role in lung health and disease. We set genome-wide significance at p<5×10−8.FindingsUK Biobank participants were recruited from March 15, 2006, to July 7, 2010. Sample selection for the UK BiLEVE study started on Nov 22, 2012, and was completed on Dec 20, 2012. We selected 50008 unique samples: 10002 individuals with low FEV1, 10000 with average FEV1, and 5002 with high FEV1 from each of the heavy smoker and never smoker groups. We noted a substantial sharing of genetic causes of low FEV1 between heavy smokers and never smokers (p=2·29×10−16) and between individuals with and without doctor-diagnosed asthma (p=6·06×10−11). We discovered six novel genome-wide significant signals of association with extremes of FEV1, including signals at four novel loci (KANSL1, TSEN54, TET2, and RBM19/TBX5) and independent signals at two previously reported loci (NPNT and HLA-DQB1/HLA-DQA2). These variants also show
AU  - Wain,LV
AU  - Shrine,N
AU  - Miller,S
AU  - Jackson,VE
AU  - Ntalla,I
AU  - Artigas,MS
AU  - Billington,CK
AU  - Kheirallah,AK
AU  - Allen,R
AU  - Cook,JP
AU  - Probert,K
AU  - Obeidat,M
AU  - Bosse,Y
AU  - Hao,K
AU  - Postma,DS
AU  - Pare,PD
AU  - Ramasamy,A
AU  - Maegi,R
AU  - Mihailov,E
AU  - Reinmaa,E
AU  - Melen,E
AU  - O'Connell,J
AU  - Frangou,E
AU  - Delaneau,O
AU  - Freeman,C
AU  - Petkova,D
AU  - McCarthy,M
AU  - Sayers,I
AU  - Deloukas,P
AU  - Hubbard,R
AU  - Pavord,I
AU  - Hansell,AL
AU  - Thomson,NC
AU  - Zeggini,E
AU  - Morris,AP
AU  - Marchini,J
AU  - Strachan,DP
AU  - Tobin,MD
AU  - Hall,IP
DO  - 10.1016/S2213-2600(15)00283-0
EP  - 781
PY  - 2015///
SN  - 2213-2619
SP  - 769
TI  - Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank
T2  - Lancet Respiratory Medicine
UR  - http://dx.doi.org/10.1016/S2213-2600(15)00283-0
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000362452900021&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/42615
VL  - 3
ER  -
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