Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-24T01:08:22.600Z Has data issue: false hasContentIssue false
  • English
  • Français

Determination of shared genetic etiology and possible causal relations between tobacco smoking and depression

Published online by Cambridge University Press:  06 April 2020

Yinghao Yao ,
Yi Xu ,
Zhen Cai ,
Qiang Liu ,
Yunlong Ma ,
Andria N. Li ,
Thomas J. Payne  and
Ming D. Li Open the ORCID record for Ming D. Li [Opens in a new window]
Yinghao Yao
Affiliation:
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Yi Xu
Affiliation:
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Zhen Cai
Affiliation:
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Qiang Liu
Affiliation:
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Yunlong Ma
Affiliation:
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Andria N. Li
Affiliation:
College of Arts and Sciences, University of Virginia, VA, USA
Thomas J. Payne
Affiliation:
Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, Jackson, MS, USA
Ming D. Li*
Affiliation:
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China Research Center for Air Pollution and Health, Zhejiang University, Hangzhou, China
*
Author for correspondence: Ming D. Li, E-mail: [email protected] or [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Backgrounds

Cigarette smoking is strongly associated with major depressive disorder (MDD). However, any genetic etiology of such comorbidity and causal relations is poorly understood, especially at the genome-wide level.

Methods

In the present in silico research, we analyzed summary data from the genome-wide association study of the Psychiatric Genetic Consortium for MDD (n = 191 005) and UK Biobank for smoking (n = 337 030) by using various biostatistical methods including Bayesian colocalization analysis, LD score regression, variant effect size correlation analysis, and Mendelian randomization (MR).

Results

By adopting a gene prioritization approach, we identified 43 genes shared by MDD and smoking, which were significantly enriched in membrane potential, gamma-aminobutyric acid receptor activity, and retrograde endocannabinoid signaling pathways, indicating that the comorbid mechanisms are involved in the neurotransmitter system. According to linkage disequilibrium score regression, we found a strong positive correlation between MDD and current smoking (rg = 0.365; p = 7.23 × 10−25) and a negative correlation between MDD and former smoking (rg = −0.298; p = 1.59 × 10−24). MR analysis suggested that genetic liability for depression increased smoking.

Conclusions

These findings inform the concomitant conditions of MDD and smoking and support the use of self-medication with smoking to counteract depression.

Keywords

Depressiongenesmolecular mechanismssmoking
Type
Original Article
Information
Psychological Medicine , Volume 51 , Issue 11 , August 2021 , pp. 1870 - 1879
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ahmed, M., Sallari, R. C., Guo, H., Moore, J. H., He, H. H., & Lupien, M. (2017). Variant set enrichment: An R package to identify disease-associated functional genomic regions. BioData Mining, 10, 9. doi: 10.1186/s13040-017-0129-5.CrossRefGoogle Scholar
Berisa, T., & Pickrell, J. K. (2016). Approximately independent linkage disequilibrium blocks in human populations. Bioinformatics (Oxford, England), 32(2), 283–285. doi: 10.1093/bioinformatics/btv546.Google ScholarPubMed
Berlin, I., & Covey, L. S. (2006). Pre-cessation depressive mood predicts failure to quit smoking: The role of coping and personality traits. Addiction, 101(12), 1814–1821. doi: 10.1111/j.1360-0443.2006.01616.x.CrossRefGoogle ScholarPubMed
Boden, J. M., Fergusson, D. M., & Horwood, L. J. (2010). Cigarette smoking and depression: Tests of causal linkages using a longitudinal birth cohort. British Journal of Psychiatry, 196(6), 440–446. doi: 10.1192/bjp.bp.109.065912.CrossRefGoogle ScholarPubMed
Bowden, J., Davey Smith, G., & Burgess, S. (2015). Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression. International Journal of Epidemiology, 44(2), 512–525. doi: 10.1093/ije/dyv080.CrossRefGoogle ScholarPubMed
Breslau, N., Kilbey, M. M., & Andreski, P. (1993). Nicotine dependence and major depression. New evidence from a prospective investigation. Archives of General Psychiatry, 50(1), 31–35. doi: 10.1001/archpsyc.1993.01820130033006.CrossRefGoogle ScholarPubMed
Breslau, N., Peterson, E. L., Schultz, L. R., Chilcoat, H. D., & Andreski, P. (1998). Major depression and stages of smoking. A longitudinal investigation. Archives of General Osychiatry, 55(2), 161–166. doi: 10.1001/archpsyc.55.2.161.CrossRefGoogle ScholarPubMed
Bulik-Sullivan, B., Finucane, H. K., Anttila, V., Gusev, A., Day, F. R., Loh, P. R., … Neale, B. M. (2015). An atlas of genetic correlations across human diseases and traits. Nature Genetics, 47(11), 1236–1241. doi: 10.1038/ng.3406.CrossRefGoogle ScholarPubMed
Burgess, S., Bowden, J., Fall, T., Ingelsson, E., & Thompson, S. G. (2017). Sensitivity analyses for robust causal inference from mendelian randomization analyses with multiple genetic variants. Epidemiology (Cambridge, Mass.), 28(1), 30–42. doi: 10.1097/EDE.0000000000000559.CrossRefGoogle ScholarPubMed
Burgess, S., Butterworth, A., & Thompson, S. G. (2013). Mendelian randomization analysis with multiple genetic variants using summarized data. Genetic Epidemiology, 37(7), 658–665. doi: 10.1002/gepi.21758.CrossRefGoogle ScholarPubMed
Carmody, T. P. (1989). Affect regulation, nicotine addiction, and smoking cessation. Journal of Psychoactive Drugs, 21(3), 331–342. doi: 10.1080/02791072.1989.10472175.CrossRefGoogle ScholarPubMed
Castillo, P. E., Younts, T. J., Chavez, A. E., & Hashimotodani, Y. (2012). Endocannabinoid signaling and synaptic function. Neuron, 76(1), 70–81. doi: 10.1016/j.neuron.2012.09.020.CrossRefGoogle ScholarPubMed
Chen, J., Bardes, E. E., Aronow, B. J., & Jegga, A. G. (2009). Toppgene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Research, 37(Web Server issue), W305–W311. doi: 10.1093/nar/gkp427.CrossRefGoogle ScholarPubMed
Chen, J., Ma, Y., Fan, R., Yang, Z., & Li, M. D. (2018). Implication of genes for the N-Methyl-D-Aspartate (NMDA) receptor in substance addictions. Molecular Neurobiology, 55(9), 7567–7578. doi: 10.1007/s12035-018-0877-3.CrossRefGoogle ScholarPubMed
Chen, Y. K., & Hsueh, Y. P. (2012). Cortactin-binding protein 2 modulates the mobility of cortactin and regulates dendritic spine formation and maintenance. Journal of Neuroscience, 32(3), 1043–1055. doi: 10.1523/JNEUROSCI.4405-11.2012.CrossRefGoogle ScholarPubMed
Cohen, S., & Lichtenstein, E. (1990). Perceived stress, quitting smoking, and smoking relapse. Health Psychology, 9(4), 466–478. doi: 10.1037//0278-6133.9.4.466.CrossRefGoogle ScholarPubMed
D'Souza, M. S., & Markou, A. (2013). The “stop” and “go” of nicotine dependence: Role of GABA and glutamate. Cold Spring Harbor Perspectives in Medicine, 3(6), 1–18. doi: 10.1101/cshperspect.a012146.CrossRefGoogle ScholarPubMed
Duman, R. S., & Aghajanian, G. K. (2012). Synaptic dysfunction in depression: Potential therapeutic targets. Science (New York, N.Y.), 338(6103), 68–72. doi: 10.1126/science.1222939.CrossRefGoogle ScholarPubMed
Duman, R. S., Aghajanian, G. K., Sanacora, G., & Krystal, J. H. (2016). Synaptic plasticity and depression: New insights from stress and rapid-acting antidepressants. Nature Medicine, 22(3), 238–249. doi: 10.1038/nm.4050.CrossRefGoogle ScholarPubMed
Ebbert, J. O., Burke, M. V., Hays, J. T., & Hurt, R. D. (2009). Combination treatment with varenicline and nicotine replacement therapy. Nicotine & Tobacco Research, 11(5), 572–576. doi: 10.1093/ntr/ntp042.CrossRefGoogle ScholarPubMed
Ebbert, J. O., Hatsukami, D. K., Croghan, I. T., Schroeder, D. R., Allen, S. S., Hays, J. T., & Hurt, R. D. (2014). Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: A randomized trial. JAMA, 311(2), 155–163. doi: 10.1001/jama.2013.283185.CrossRefGoogle ScholarPubMed
Finci, L., Zhang, Y., Meijers, R., & Wang, J. H. (2015). Signaling mechanism of the netrin-1 receptor DCC in axon guidance. Progress in Biophysics & Molecular Biology, 118(3), 153–160. doi: 10.1016/j.pbiomolbio.2015.04.001.CrossRefGoogle ScholarPubMed
Gerhard, D. M., Wohleb, E. S., & Duman, R. S. (2016). Emerging treatment mechanisms for depression: Focus on glutamate and synaptic plasticity. Drug Discovery Today, 21(3), 454–464. doi: 10.1016/j.drudis.2016.01.016.CrossRefGoogle ScholarPubMed
Goodman, E., & Capitman, J. (2000). Depressive symptoms and cigarette smoking among teens. Pediatrics, 106(4), 748–755. doi: 10.1542/peds.106.4.748.CrossRefGoogle ScholarPubMed
Gorzalka, B. B., & Hill, M. N. (2011). Putative role of endocannabinoid signaling in the etiology of depression and actions of antidepressants. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 35(7), 1575–1585. doi: 10.1016/j.pnpbp.2010.11.021.CrossRefGoogle ScholarPubMed
Guney, E., Garcia-Garcia, J., & Oliva, B. (2014). GUILDify: A web server for phenotypic characterization of genes through biological data integration and network-based prioritization algorithms. Bioinformatics (Oxford, England), 30(12), 1789–1790. doi: 10.1093/bioinformatics/btu092.CrossRefGoogle ScholarPubMed
Hall, S. M., & Prochaska, J. J. (2009). Treatment of smokers with co-occurring disorders: Emphasis on integration in mental health and addiction treatment settings. Annual Review of Clinical Psychology, 5, 409–431. doi: 10.1146/annurev.clinpsy.032408.153614.CrossRefGoogle ScholarPubMed
Hemani, G., Zheng, J., Elsworth, B., Wade, K. H., Haberland, V., Baird, D., … Haycock, P. C. (2018). The MR-Base platform supports systematic causal inference across the human phenome. Elife, 7, e34408. doi: 10.7554/eLife.34408.CrossRefGoogle ScholarPubMed
Hillard, C. J., Weinlander, K. M., & Stuhr, K. L. (2012). Contributions of endocannabinoid signaling to psychiatric disorders in humans: Genetic and biochemical evidence. Neuroscience, 204, 207–229. doi: 10.1016/j.neuroscience.2011.11.020.CrossRefGoogle ScholarPubMed
Hitsman, B., Borrelli, B., McChargue, D. E., Spring, B., & Niaura, R. (2003). History of depression and smoking cessation outcome: A meta-analysis. Journal of Consulting and Clinical Psychology, 71(4), 657–663. doi: 10.1037/0022-006x.71.4.657.CrossRefGoogle ScholarPubMed
Hu, M. C., Davies, M., & Kandel, D. B. (2006). Epidemiology and correlates of daily smoking and nicotine dependence among young adults in the United States. American Journal of Public Health, 96(2), 299–308. doi: 10.2105/AJPH.2004.057232.CrossRefGoogle ScholarPubMed
Issa, J. S., Abe, T. O., Moura, S., Santos, P. C., & Pereira, A. C. (2013). Effectiveness of coadministration of varenicline, bupropion, and serotonin reuptake inhibitors in a smoking cessation program in the real-life setting. Nicotine & Tobacco Research, 15(6), 1146–1150. doi: 10.1093/ntr/nts230.CrossRefGoogle Scholar
Johnson, E. O., Rhee, S. H., Chase, G. A., & Breslau, N. (2004). Comorbidity of depression with levels of smoking: An exploration of the shared familial risk hypothesis. Nicotine & Tobacco Research, 6(6), 1029–1038. doi: 10.1080/14622200412331324901.Google ScholarPubMed
Kano, M., Ohno-Shosaku, T., Hashimotodani, Y., Uchigashima, M., & Watanabe, M. (2009). Endocannabinoid-mediated control of synaptic transmission. Physiological Reviews, 89(1), 309–380. doi: 10.1152/physrev.00019.2008.CrossRefGoogle ScholarPubMed
Kendler, K. S., Neale, M. C., MacLean, C. J., Heath, A. C., Eaves, L. J., & Kessler, R. C. (1993). Smoking and major depression. A causal analysis. Archives of General Psychiatry, 50(1), 36–43. doi: 10.1001/archpsyc.1993.01820130038007.CrossRefGoogle ScholarPubMed
Koegelenberg, C. F., Noor, F., Bateman, E. D., van Zyl-Smit, R. N., Bruning, A., O'Brien, J. A., … Irusen, E. M. (2014). Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation: A randomized clinical trial. JAMA, 312(2), 155–161. doi: 10.1001/jama.2014.7195.CrossRefGoogle ScholarPubMed
Kopetz, C., MacPherson, L., Mitchell, A. D., Houston-Ludlam, A. N., & Wiers, R. W. (2017). A novel training approach to activate alternative behaviors for smoking in depressed smokers. Experimental and Clinical Psychopharmacology, 25(1), 50–60. doi: 10.1037/pha0000108.CrossRefGoogle ScholarPubMed
Lango Allen, H., Estrada, K., Lettre, G., Berndt, S. I., Weedon, M. N., Rivadeneira, F., … Hirschhorn, J. N. (2010). Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature, 467(7317), 832–838. doi: 10.1038/nature09410.CrossRefGoogle ScholarPubMed
Lasser, K., Boyd, J. W., Woolhandler, S., Himmelstein, D. U., McCormick, D., & Bor, D. H. (2000). Smoking and mental illness: A population-based prevalence study. JAMA, 284(20), 2606–2610. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11086367.CrossRefGoogle ScholarPubMed
Leite, C. E., Mocelin, C. A., Petersen, G. O., Leal, M. B., & Thiesen, F. V. (2009). Rimonabant: An antagonist drug of the endocannabinoid system for the treatment of obesity. Pharmacological Reports, 61(2), 217–224. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/19443932.CrossRefGoogle ScholarPubMed
Li, M. D. (2018). Tobacco smoking addiction: Epdemiology, genetics, mechanisms, and treatment. Singapore: Springer.Google Scholar
Liu, M., Jiang, Y., Wedow, R., Li, Y., Brazel, D. M., Chen, F., … Vrieze, S. (2019). Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. Nature Genetics, 51(2), 237–244. doi: 10.1038/s41588-018-0307-5.CrossRefGoogle ScholarPubMed
Payne, T. J., Ma, J. Z., Crews, K. M., & Li, M. D. (2013). Depressive symptoms among heavy cigarette smokers: The influence of daily rate, gender, and race. Nicotine & Tobacco Research, 15(10), 1714–1721. doi: 10.1093/ntr/ntt047.CrossRefGoogle ScholarPubMed
Pickrell, J. K., Berisa, T., Liu, J. Z., Segurel, L., Tung, J. Y., & Hinds, D. A. (2016). Detection and interpretation of shared genetic influences on 42 human traits. Nature Genetics, 48(7), 709–717. doi: 10.1038/ng.3570.CrossRefGoogle ScholarPubMed
Piper, M. E., Schlam, T. R., Cook, J. W., Smith, S. S., Bolt, D. M., Loh, W. Y., … Baker, T. B. (2017). Toward precision smoking cessation treatment I: Moderator results from a factorial experiment. Drug and Alcohol Dependence, 171, 59–65. doi: 10.1016/j.drugalcdep.2016.11.025.CrossRefGoogle ScholarPubMed
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A., Bender, D., … Sham, P. C. (2007). PLINK: A tool set for whole-genome association and population-based linkage analyses. American Journal of Human Genetics, 81(3), 559–575. doi: S0002-9297(07)61352-4 [pii] 10.1086/519795.CrossRefGoogle ScholarPubMed
Reich, C. G., Taylor, M. E., & McCarthy, M. M. (2009). Differential effects of chronic unpredictable stress on hippocampal CB1 receptors in male and female rats. Behavioural Brain Research, 203(2), 264–269. doi: 10.1016/j.bbr.2009.05.013.CrossRefGoogle ScholarPubMed
Shoaib, M., & Buhidma, Y. (2018). Why are antidepressant drugs effective smoking cessation aids? Current Neuropharmacology, 16(4), 426–437. doi: 10.2174/1570159X15666170915142122.CrossRefGoogle ScholarPubMed
Singh, K., Loreth, D., Pottker, B., Hefti, K., Innos, J., Schwald, K., … Schafer, M. K. E. (2018). Neuronal growth and behavioral alterations in mice deficient for the psychiatric disease-associated Negr1 gene. Frontiers in Molecular Neuroscience, 11, 30. doi: 10.3389/fnmol.2018.00030.CrossRefGoogle ScholarPubMed
Smith, G. D., & Ebrahim, S. (2003). 'Mendelian randomization': Can genetic epidemiology contribute to understanding environmental determinants of disease? International Journal of Epidemiology, 32(1), 1–22. doi: 10.1093/ije/dyg070.CrossRefGoogle ScholarPubMed
Tang, A. H., Karson, M. A., Nagode, D. A., McIntosh, J. M., Uebele, V. N., Renger, J. J., … Alger, B. E. (2011). Nerve terminal nicotinic acetylcholine receptors initiate quantal GABA release from perisomatic interneurons by activating axonal T-type (Cav3) Ca(2)(+) channels and Ca(2)(+) release from stores. Journal of Neuroscience, 31(38), 13546–13561. doi: 10.1523/JNEUROSCI.2781-11.2011.CrossRefGoogle ScholarPubMed
Tulloch, H. E., Pipe, A. L., Clyde, M. J., Reid, R. D., & Els, C. (2016). The quit experience and concerns of smokers with psychiatric illness. American Journal of Preventive Medicine, 50(6), 709–718. doi: 10.1016/j.amepre.2015.11.006.CrossRefGoogle ScholarPubMed
Windle, M., & Windle, R. C. (2001). Depressive symptoms and cigarette smoking among middle adolescents: Prospective associations and intrapersonal and interpersonal influences. Journal of Consulting and Clinical Psychology, 69(2), 215–226. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11393599.CrossRefGoogle ScholarPubMed
Wonnacott, S. (1997). Presynaptic nicotinic ACh receptors. Trends in Neurosciences, 20(2), 92–98. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9023878.CrossRefGoogle ScholarPubMed
Wootton, R. E., Richmond, R. C., Stuijfzand, B. G., Lawn, R. B., Sallis, H. M., Taylor, G. M. J., … Munafo, M. R. (2019). Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: A Mendelian randomisation study. Psychological Medicine, 1–9. doi: 10.1017/S0033291719002678.Google ScholarPubMed
Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., … Major Depressive Disorder Working Group of the Psychiatric Genomics, C. (2018). Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nature Genetics, 50(5), 668–681. doi:10.1038/s41588-018-0090-3.CrossRefGoogle ScholarPubMed
Wu, L. T., & Anthony, J. C. (1999). Tobacco smoking and depressed mood in late childhood and early adolescence. American Journal of Public Health, 89(12), 1837–1840. doi: 10.2105/ajph.89.12.1837.CrossRefGoogle ScholarPubMed
Yang, J., & Li, M. D. (2016). Converging findings from linkage and association analyses on susceptibility genes for smoking and other addictions. Molecular Psychiatry, 21(8), 992–1008. doi: 10.1038/mp.2016.67.CrossRefGoogle ScholarPubMed
Zhang, B., Kirov, S., & Snoddy, J. (2005). Webgestalt: An integrated system for exploring gene sets in various biological contexts. Nucleic Acids Research, 33(Web Server issue), W741–W748. doi: 10.1093/nar/gki475.CrossRefGoogle ScholarPubMed
Zheng, J., Erzurumluoglu, A. M., Elsworth, B. L., Kemp, J. P., Howe, L., Haycock, P. C., … Neale, B. M. (2017). LD Hub: A centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. Bioinformatics (Oxford, England), 33(2), 272–279. doi: 10.1093/bioinformatics/btw613.CrossRefGoogle ScholarPubMed
Zvolensky, M. J., Bakhshaie, J., Sheffer, C., Perez, A., & Goodwin, R. D. (2015). Major depressive disorder and smoking relapse among adults in the United States: A 10-year, prospective investigation. Psychiatry Research, 226(1), 73–77. doi: 10.1016/j.psychres.2014.11.064.CrossRefGoogle ScholarPubMed
Supplementary material: File

Yao et al. Supplementary Materials

Yao et al. Supplementary Materials 1

Download Yao et al. Supplementary Materials(File)
File 31.1 KB
Supplementary material: File

Yao et al. Supplementary Materials

Yao et al. Supplementary Materials 2

Download Yao et al. Supplementary Materials(File)
File 340 KB