Sebastian-Edgar Baumeister1, Hansjörg Baurecht2, Michael Nolde3, Zoheir Alayash4, Sven Gläser5, Mattias Johansson6, Christopher I Amos7, Emma C Johnson8, Rayjean J Hung9. 1. Department of Epidemiology, Ludwig-Maximilian University of Munich, University Center for Health Sciences at the Klinikum (UNIKA-T) Augsburg, Augsburg, Germany; Independent Research Group Clinical Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany; Institute of Health Services Research in Dentistry, University of Münster, Münster, Germany. Electronic address: sebastian.baumeister@uni-muenster.de. 2. Department of Epidemiology and Preventive Medicine, University of Regensburg, Germany. 3. Department of Epidemiology, Ludwig-Maximilian University of Munich, University Center for Health Sciences at the Klinikum (UNIKA-T) Augsburg, Augsburg, Germany; Independent Research Group Clinical Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany. 4. Department of Epidemiology, Ludwig-Maximilian University of Munich, University Center for Health Sciences at the Klinikum (UNIKA-T) Augsburg, Augsburg, Germany. 5. Department of Internal Medicine B Cardiology, Intensive Care, Pulmonary Medicine, and Infectious Diseases, University Medicine Greifswald, Greifswald, Germany; Vivantes Klinikum Neukölln und Spandau, Klinik für Innere Medizin-Pneumologie und Infektiologie, Berlin, Germany. 6. Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France. 7. Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas. 8. Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri. 9. Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada; Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Abstract
INTRODUCTION: Because of widespread use, understanding the pulmonary effects of cannabis use is important; but its role independent from tobacco smoking is yet to be elucidated. We used Mendelian randomization (MR) to assess the effect of genetic liability to lifetime cannabis use and cannabis use disorder on pulmonary function and lung cancer. METHODS: We used four single nucleotide polymorphisms associated with lifetime cannabis use (p value <5 × 10-8) from a genome-wide association study (GWAS) of 184,765 individuals of European descent from the International Cannabis Consortium, 23andme, and U.K. Biobank as instrumental variables. Seven single nucleotide polymorphisms (p value <5 × 10-8) were selected as instruments for cannabis use disorder from a GWAS meta-analysis of 17,068 European ancestry cases and 357,219 controls of European descent from Psychiatric Genomics Consortium Substance Use Disorders working group, Lundbeck Foundation Initiative for Integrative PsychiatricResearch, and deCode. To assess lung function, GWAS included 79,055 study participants of the SpiroMeta Consortium, and for lung cancer GWAS from the International Lung Cancer Consortium contained 29,266 cases and 56,450 controls. RESULTS: MR revealed that genetic liability to lifetime cannabis use was associated with increased risk of squamous cell carcinoma (OR = 1.22, 95%, confidence interval = 1.07-1.39, p value = 0.003, q value = 0.025). Pleiotropy-robust methods and positive and negative control analyses did not indicate bias in the primary analysis. CONCLUSIONS: The findings of this MR analysis suggest evidence for a potential causal association between genetic liability for cannabis use and the risk of squamous cell carcinoma. Triangulating MR and observational studies and addressing orthogonal sources of bias are necessary to confirm this finding.
INTRODUCTION: Because of widespread use, understanding the pulmonary effects of cannabis use is important; but its role independent from tobacco smoking is yet to be elucidated. We used Mendelian randomization (MR) to assess the effect of genetic liability to lifetime cannabis use and cannabis use disorder on pulmonary function and lung cancer. METHODS: We used four single nucleotide polymorphisms associated with lifetime cannabis use (p value <5 × 10-8) from a genome-wide association study (GWAS) of 184,765 individuals of European descent from the International Cannabis Consortium, 23andme, and U.K. Biobank as instrumental variables. Seven single nucleotide polymorphisms (p value <5 × 10-8) were selected as instruments for cannabis use disorder from a GWAS meta-analysis of 17,068 European ancestry cases and 357,219 controls of European descent from Psychiatric Genomics Consortium Substance Use Disorders working group, Lundbeck Foundation Initiative for Integrative PsychiatricResearch, and deCode. To assess lung function, GWAS included 79,055 study participants of the SpiroMeta Consortium, and for lung cancer GWAS from the International Lung Cancer Consortium contained 29,266 cases and 56,450 controls. RESULTS: MR revealed that genetic liability to lifetime cannabis use was associated with increased risk of squamous cell carcinoma (OR = 1.22, 95%, confidence interval = 1.07-1.39, p value = 0.003, q value = 0.025). Pleiotropy-robust methods and positive and negative control analyses did not indicate bias in the primary analysis. CONCLUSIONS: The findings of this MR analysis suggest evidence for a potential causal association between genetic liability for cannabis use and the risk of squamous cell carcinoma. Triangulating MR and observational studies and addressing orthogonal sources of bias are necessary to confirm this finding.
Authors: Pablo Roman; Ana Ortiz-Rodriguez; Ana Romero-Lopez; Miguel Rodriguez-Arrastia; Carmen Ropero-Padilla; Nuria Sanchez-Labraca; Lola Rueda-Ruzafa Journal: Healthcare (Basel) Date: 2021-12-31