Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank

Wain, Louise V.; Shrine, Nick; Miller, Suzanne; Jackson, Victoria E.; Ntalla, Ioanna; Artigas, Mar�a Soler; Billington, Charlotte K.; Kheirallah, Abdul Kader; Allen, Richard; Cook, James P.; Probert, Kelly; Obeidat, Ma'en; Boss�, Yohan; Hao, Ke; Postma, Dirkje S.; Par�, Peter D.; Ramasamy, Adaikalavan; M�gi, Reedik; Mihailov, Evelin; Reinmaa, Eva; Mel�n, Erik; O'Connell, Jared; Frangou, Eleni; Delaneau, Olivier; Freeman, Colin; Petkova, Desislava; McCarthy, Mark; Sayers, Ian; Deloukas, Panos; Hubbard, Richard; Pavord, Ian; Hansell, Anna L.; Thomson, Neil C.; Zeggini, Eleftheria; Morris, Andrew P.; Marchini, Jonathan; Strachan, David P.; Tobin, Martin D.; Hall, Ian P.

Abstract

Background

Understanding 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.

Methods

We 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

• Journal Article Type: Article
• Publication Date: Oct 1, 2015
• Deposit Date: Apr 5, 2016
• Publicly Available Date: Apr 5, 2016
• Journal: Lancet Respiratory Medicine
• Print ISSN: 2213-2600
• Electronic ISSN: 2213-2619
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Issue: 10
• DOI: https://doi.org/10.1016/S2213-2600%2815%2900283-0
• Public URL: https://nottingham-repository.worktribe.com/output/982035
• Publisher URL: http://dx.doi.org/10.1016/S2213-2600(15)00283-0