S76 Mendelian randomization study of cigarette smoking in idiopathic pulmonary fibrosis

Introduction and ObjectivesA cigarette smoking – idiopathic pulmonary fibrosis (IPF) association has been observed in several case-control studies. However, it is not known whether smoking causes IPF or if the observed association arises as a result of confounding (for example many studies have used...

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Veröffentlicht in:Thorax 2021-02, Vol.76 (Suppl 1), p.A47-A48
Hauptverfasser: Reynolds, CJ, Yates, TA, Gill, D, Cullinan, P
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Yates, TA
Gill, D
Cullinan, P
description Introduction and ObjectivesA cigarette smoking – idiopathic pulmonary fibrosis (IPF) association has been observed in several case-control studies. However, it is not known whether smoking causes IPF or if the observed association arises as a result of confounding (for example many studies have used population controls and may be vulnerable to selection bias).Mendelian randomization can offer an opportunity to investigate causality between cigarette smoking and IPF.MethodsGenetic instruments for lifetime smoking score[1] (taking into account smoking duration and heaviness) were obtained from a genome-wide association study (GWAS) performed in UK Biobank (462,690 individuals, European ancestry). We used variants that were significantly associated with smoking at p
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However, it is not known whether smoking causes IPF or if the observed association arises as a result of confounding (for example many studies have used population controls and may be vulnerable to selection bias).Mendelian randomization can offer an opportunity to investigate causality between cigarette smoking and IPF.MethodsGenetic instruments for lifetime smoking score[1] (taking into account smoking duration and heaviness) were obtained from a genome-wide association study (GWAS) performed in UK Biobank (462,690 individuals, European ancestry). We used variants that were significantly associated with smoking at p&lt;5 × 10-8, which together explained 0.36% percent of variation in lifetime smoking. GWAS summary data for IPF were obtained from The Collaborative Group of genetic studies of IPF[2](2,668 IPF cases and 8,591 controls, European ancestry). Analysis was performed using the TwoSampleMR package of R.Results118 variants were used as instruments. In the main analysis, the odds ratio per standard deviation increase in lifetime smoking score was 0.6 (95%CI 0.4–1, p=0.07). Similar results were obtained in statistical sensitivity analyses.Abstract S76 Figure 1ConclusionsThis Mendelian randomization analysis does not provide evidence to support the notion that smoking causes IPF. It may be that confounding is responsible for the association in observational studies. Clearly, there is a strong case for stopping smoking for other reasons.ReferencesWootton RE, Richmond RC, Stuijfzand BG, Lawn RB, Sallis HM, Taylor GM, Hemani G, Jones HJ, Zammit S, Smith GD, Munafò MR. Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study. Psychological Medicine 2019 Nov 6:1–9.Allen RJ, Guillen-Guio B, Oldham JM, Ma SF, Dressen A, Paynton ML, Kraven LM, Obeidat ME, Li X, Ng M, Braybrooke R. Genome-wide association study of susceptibility to idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine 2020 Mar 1;201(5):564–74.</description><identifier>ISSN: 0040-6376</identifier><identifier>EISSN: 1468-3296</identifier><identifier>DOI: 10.1136/thorax-2020-BTSabstracts.81</identifier><language>eng</language><publisher>London: BMJ Publishing Group LTD</publisher><subject>Genomes ; Pulmonary fibrosis ; Smoking</subject><ispartof>Thorax, 2021-02, Vol.76 (Suppl 1), p.A47-A48</ispartof><rights>Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2021 Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27925,27926</link.rule.ids></links><search><creatorcontrib>Reynolds, CJ</creatorcontrib><creatorcontrib>Yates, TA</creatorcontrib><creatorcontrib>Gill, D</creatorcontrib><creatorcontrib>Cullinan, P</creatorcontrib><title>S76 Mendelian randomization study of cigarette smoking in idiopathic pulmonary fibrosis</title><title>Thorax</title><description>Introduction and ObjectivesA cigarette smoking – idiopathic pulmonary fibrosis (IPF) association has been observed in several case-control studies. However, it is not known whether smoking causes IPF or if the observed association arises as a result of confounding (for example many studies have used population controls and may be vulnerable to selection bias).Mendelian randomization can offer an opportunity to investigate causality between cigarette smoking and IPF.MethodsGenetic instruments for lifetime smoking score[1] (taking into account smoking duration and heaviness) were obtained from a genome-wide association study (GWAS) performed in UK Biobank (462,690 individuals, European ancestry). We used variants that were significantly associated with smoking at p&lt;5 × 10-8, which together explained 0.36% percent of variation in lifetime smoking. GWAS summary data for IPF were obtained from The Collaborative Group of genetic studies of IPF[2](2,668 IPF cases and 8,591 controls, European ancestry). Analysis was performed using the TwoSampleMR package of R.Results118 variants were used as instruments. In the main analysis, the odds ratio per standard deviation increase in lifetime smoking score was 0.6 (95%CI 0.4–1, p=0.07). Similar results were obtained in statistical sensitivity analyses.Abstract S76 Figure 1ConclusionsThis Mendelian randomization analysis does not provide evidence to support the notion that smoking causes IPF. It may be that confounding is responsible for the association in observational studies. Clearly, there is a strong case for stopping smoking for other reasons.ReferencesWootton RE, Richmond RC, Stuijfzand BG, Lawn RB, Sallis HM, Taylor GM, Hemani G, Jones HJ, Zammit S, Smith GD, Munafò MR. Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study. Psychological Medicine 2019 Nov 6:1–9.Allen RJ, Guillen-Guio B, Oldham JM, Ma SF, Dressen A, Paynton ML, Kraven LM, Obeidat ME, Li X, Ng M, Braybrooke R. Genome-wide association study of susceptibility to idiopathic pulmonary fibrosis. 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However, it is not known whether smoking causes IPF or if the observed association arises as a result of confounding (for example many studies have used population controls and may be vulnerable to selection bias).Mendelian randomization can offer an opportunity to investigate causality between cigarette smoking and IPF.MethodsGenetic instruments for lifetime smoking score[1] (taking into account smoking duration and heaviness) were obtained from a genome-wide association study (GWAS) performed in UK Biobank (462,690 individuals, European ancestry). We used variants that were significantly associated with smoking at p&lt;5 × 10-8, which together explained 0.36% percent of variation in lifetime smoking. GWAS summary data for IPF were obtained from The Collaborative Group of genetic studies of IPF[2](2,668 IPF cases and 8,591 controls, European ancestry). Analysis was performed using the TwoSampleMR package of R.Results118 variants were used as instruments. In the main analysis, the odds ratio per standard deviation increase in lifetime smoking score was 0.6 (95%CI 0.4–1, p=0.07). Similar results were obtained in statistical sensitivity analyses.Abstract S76 Figure 1ConclusionsThis Mendelian randomization analysis does not provide evidence to support the notion that smoking causes IPF. It may be that confounding is responsible for the association in observational studies. Clearly, there is a strong case for stopping smoking for other reasons.ReferencesWootton RE, Richmond RC, Stuijfzand BG, Lawn RB, Sallis HM, Taylor GM, Hemani G, Jones HJ, Zammit S, Smith GD, Munafò MR. Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study. Psychological Medicine 2019 Nov 6:1–9.Allen RJ, Guillen-Guio B, Oldham JM, Ma SF, Dressen A, Paynton ML, Kraven LM, Obeidat ME, Li X, Ng M, Braybrooke R. Genome-wide association study of susceptibility to idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine 2020 Mar 1;201(5):564–74.</abstract><cop>London</cop><pub>BMJ Publishing Group LTD</pub><doi>10.1136/thorax-2020-BTSabstracts.81</doi></addata></record>
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Pulmonary fibrosis
Smoking
title S76 Mendelian randomization study of cigarette smoking in idiopathic pulmonary fibrosis
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