Allergic rhinitis (AR) is a non-infectious chronic inflammatory disease of the nasal mucosa mediated mainly by immunoglobulin E (IgE) in atopic individuals after exposure to allergens, with the typical symptoms of paroxysmal sneezing, watery runny nose, itchy nose and nasal congestion. Mendelian randomization (MR), an innovative epidemiological approach that uses common genetic variants as instrumental variables for exposure, thus enabling prediction of their causal relationship with outcomes, has been widely used in recent years in studies related to AR. This paper provides a review of the method and its progress in the field of allergic rhinitis research.
References
[1]
Chinese Journal of Otorhinolaryngology, Head and Neck Surgery, Editorial Committee, Rhinology Group, Chinese Medical Association, Otorhinolaryngology, Head and Neck Surgery Branch, Rhinology Group (2022) Chinese Guidelines for the Diagnosis and Treatment of Allergic Rhinitis (2022, Revised Edition). ChineseJournalofOtolaryngology, HeadandNeckSurgery, 57, 106-129.
[2]
Brożek, J.L., Bousquet, J., Baena-Cagnani, C.E., Bonini, S., Canonica, G.W., Casale, T.B., et al. (2010) Allergic Rhinitis and Its Impact on Asthma (ARIA) Guidelines: 2010 Revision. JournalofAllergyandClinicalImmunology, 126, 466-476. https://doi.org/10.1016/j.jaci.2010.06.047
[3]
Bousquet, J., Khaltaev, N., Cruz, A.A., et al. (2008) Allergic Rhinitis and Its Impact on Asthma (ARIA) 2008 Update (in Collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy, 63, 8-160.
Hingorani, A. and Humphries, S. (2005) Nature’s Randomised Trials. TheLancet, 366, 1906-1908. https://doi.org/10.1016/s0140-6736(05)67767-7
[6]
Chen, Y., Xu, X., Wang, L., Li, K., Sun, Y., Xiao, L., et al. (2022) Genetic Insights into Therapeutic Targets for Aortic Aneurysms: A Mendelian Randomization Study. eBioMedicine, 83, Article ID: 104199. https://doi.org/10.1016/j.ebiom.2022.104199
[7]
Chen, Y., Sun, Y., Wang, L., Xu, K. and Wang, D.W. (2024) Genetic Insights into Associations of Multisite Chronic Pain with Common Diseases and Biomarkers Using Data from the UK Biobank. BritishJournalofAnaesthesia, 132, 372-382. https://doi.org/10.1016/j.bja.2023.11.007
[8]
Emdin, C.A., Khera, A.V. and Kathiresan, S. (2017) Mendelian Randomization. JAMA, 318, 1925-1926. https://doi.org/10.1001/jama.2017.17219
[9]
Davey Smith, G. and Ebrahim, S. (2003) “Mendelian Randomization”: Can Genetic Epidemiology Contribute to Understanding Environmental Determinants of Disease? InternationalJournalofEpidemiology, 32, 1-22. https://doi.org/10.1093/ije/dyg070
[10]
Neeland, I.J. and Kozlitina, J. (2017) Mendelian Randomization: Using Natural Genetic Variation to Assess the Causal Role of Modifiable Risk Factors in Observational Studies. Circulation, 135, 755-758. https://doi.org/10.1161/circulationaha.117.026857
[11]
Burgess, S. and Thompson, S.G. (2011) Avoiding Bias from Weak Instruments in Mendelian Randomization Studies. InternationalJournalofEpidemiology, 40, 755-764. https://doi.org/10.1093/ije/dyr036
[12]
Verbanck, M., Chen, C., Neale, B. and Do, R. (2018) Detection of Widespread Horizontal Pleiotropy in Causal Relationships Inferred from Mendelian Randomization between Complex Traits and Diseases. NatureGenetics, 50, 693-698. https://doi.org/10.1038/s41588-018-0099-7
[13]
Sekula, P., Del Greco M, F., Pattaro, C. and Köttgen, A. (2016) Mendelian Randomization as an Approach to Assess Causality Using Observational Data. JournaloftheAmericanSocietyofNephrology, 27, 3253-3265. https://doi.org/10.1681/asn.2016010098
[14]
Zuccolo, L. and Holmes, M.V. (2016) Commentary: Mendelian Randomization-Inspired Causal Inference in the Absence of Genetic Data. InternationalJournalofEpidemiology, 46, 962-965. https://doi.org/10.1093/ije/dyw327
[15]
Li, J.M., Fan, N. and Wang, X. (2024) Research Progress of Mendelian Randomization Analysis in Obstructive Sleep Apnea. ChineseJournalofOtorhinolaryngology—HeadandNeckSurgery, 59, 774-781.
[16]
Wang, Y.Z. and Shen, H.B. (2020) Challenges and Factors That Influencing Causal Inference and Interpretation, Based on Mendelian Randomization Studies. Chinese JournalofEpidemiology, 41, 1231-1236.
[17]
Licari, A., Castagnoli, R., Denicolò, C.F., Rossini, L., Marseglia, A. and Marseglia, G.L. (2017) The Nose and the Lung: United Airway Disease? FrontiersinPediatrics, 5, Article No. 44. https://doi.org/10.3389/fped.2017.00044
[18]
Brożek, J.L., Bousquet, J., Agache, I., Agarwal, A., Bachert, C., Bosnic-Anticevich, S., et al. (2017) Allergic Rhinitis and Its Impact on Asthma (ARIA) Guidelines—2016 Revision. JournalofAllergyandClinicalImmunology, 140, 950-958. https://doi.org/10.1016/j.jaci.2017.03.050
[19]
Ramakrishnan, J.B., Kingdom, T.T. and Ramakrishnan, V.R. (2013) Allergic Rhinitis and Chronic Rhinosinusitis: Their Impact on Lower Airways. ImmunologyandAllergyClinicsofNorthAmerica, 33, 45-60. https://doi.org/10.1016/j.iac.2012.10.009
[20]
Samitas, K., Carter, A., Kariyawasam, H.H. and Xanthou, G. (2017) Upper and Lower Airway Remodelling Mechanisms in Asthma, Allergic Rhinitis and Chronic Rhinosinusitis: The One Airway Concept Revisited. Allergy, 73, 993-1002. https://doi.org/10.1111/all.13373
[21]
Eriksson, J., Bjerg, A., Lötvall, J., Wennergren, G., Rönmark, E., Torén, K., et al. (2011) Rhinitis Phenotypes Correlate with Different Symptom Presentation and Risk Factor Patterns of Asthma. RespiratoryMedicine, 105, 1611-1621. https://doi.org/10.1016/j.rmed.2011.06.004
[22]
Lombardi, C., Passalacqua, G., Gargioni, S., Senna, G., Ciprandi, G., Scordamaglia, A., et al. (2001) The Natural History of Respiratory Allergy: A Follow-Up Study of 99 Patients up to 10 Years. RespiratoryMedicine, 95, 9-12. https://doi.org/10.1053/rmed.2000.0945
[23]
Zhang, Z., Li, G., Zhou, S., Wang, M., Yu, L. and Jiang, Y. (2024) Causal Effects of Asthma on Upper Airway Diseases and Allergic Diseases: A Two-Sample Mendelian Randomization. InternationalArchivesofAllergyandImmunology, 2024, 1-10. https://doi.org/10.1159/000540358
[24]
Zhang, Z., Li, G., Yu, L., Jiang, J., Zhou, S. and Jiang, Y. (2023) Using a Two-Sample Mendelian Randomization Study Based on Genome-Wide Association Studies to Assess and Demonstrate the Causal Effects of Allergic Rhinitis on Chronic Lower Respiratory Diseases and Lung Function. InternationalArchivesofAllergyandImmunology, 184, 311-319. https://doi.org/10.1159/000528350
[25]
Nelson, R.W., Geha, R.S. and McDonald, D.R. (2022) Inborn Errors of the Immune System Associated with Atopy. FrontiersinImmunology, 13, Article ID: 860821. https://doi.org/10.3389/fimmu.2022.860821
[26]
Zhao, J., Zhang, M. and Li, Z. (2023) Association between Immune-Related Disease and Allergic Rhinitis: A Two-Sample Mendelian Randomization Study. AmericanJournalofRhinology&Allergy, 38, 31-37. https://doi.org/10.1177/19458924231207131
[27]
Novembre, E., Cianferoni, A., Lombardi, E., Bernardini, R., Pucci, N. and Vierucci, A. (2001) Natural History of “Intrinsic” Atopic Dermatitis. Allergy, 56, 452-453. https://doi.org/10.1034/j.1398-9995.2001.056005452.x
[28]
Wüthrich, B. and Schmid‐Grendelmeier, P. (2002) Natural Course of AEDS. Allergy, 57, 267-268. https://doi.org/10.1034/j.1398-9995.2002.1n3572.x
[29]
Myrelid, P., Dufmats, M., Lilja, I., Grännö, C., Lannerstad, O. and Sjödahl, R. (2004) Atopic Manifestations Are More Common in Patients with Crohn Disease than in the General Population. ScandinavianJournalofGastroenterology, 39, 731-736. https://doi.org/10.1080/00365520410005955
[30]
Radon, K., Windstetter, D., Poluda, A.L., Mueller, B., Mutius, E.v. and Koletzko, S. (2007) Contact with Farm Animals in Early Life and Juvenile Inflammatory Bowel Disease: A Case-Control Study. Pediatrics, 120, 354-361. https://doi.org/10.1542/peds.2006-3624
[31]
Li, J., Wang, L., Ma, Y. and Liu, Y. (2024) Inflammatory Bowel Disease and Allergic Diseases: A Mendelian Randomization Study. PediatricAllergyandImmunology, 35, e14147. https://doi.org/10.1111/pai.14147
[32]
Lee, E., Lee, S., Kang, M., Kim, K., Won, S., Kim, B., et al. (2016) Clostridia in the Gut and Onset of Atopic Dermatitis via Eosinophilic Inflammation. AnnalsofAllergy, Asthma&Immunology, 117, 91-92.e1. https://doi.org/10.1016/j.anai.2016.04.019
[33]
Galazzo, G., van Best, N., Bervoets, L., Dapaah, I.O., Savelkoul, P.H., Hornef, M.W., et al. (2020) Development of the Microbiota and Associations with Birth Mode, Diet, and Atopic Disorders in a Longitudinal Analysis of Stool Samples, Collected from Infancy through Early Childhood. Gastroenterology, 158, 1584-1596. https://doi.org/10.1053/j.gastro.2020.01.024
[34]
Watts, A.M., West, N.P., Zhang, P., Smith, P.K., Cripps, A.W. and Cox, A.J. (2020) The Gut Microbiome of Adults with Allergic Rhinitis Is Characterised by Reduced Diversity and an Altered Abundance of Key Microbial Taxa Compared to Controls. InternationalArchivesofAllergyandImmunology, 182, 94-105. https://doi.org/10.1159/000510536
[35]
Jin, Q., Ren, F., Dai, D., Sun, N., Qian, Y. and Song, P. (2023) The Causality between Intestinal Flora and Allergic Diseases: Insights from a Bi-Directional Two-Sample Mendelian Randomization Analysis. Frontiers in Immunology, 14, Article ID: 1121273. https://doi.org/10.3389/fimmu.2023.1121273
[36]
Jiang, N., Zhao, J., Zhou, C. and Nan, X. (2024) Circulating Interleukin-27 Is Associated with the Risk of Chronic Periodontitis and Allergic Rhinitis: A Mendelian Randomization Analysis. Autoimmunity, 57, Article ID: 2358070. https://doi.org/10.1080/08916934.2024.2358070
[37]
Zhang, X., Wang, P., Dang, Q., Huang, X., Xiao, Y. and Guan, B. (2024) Inflammatory Cytokines and Risk of Allergic Rhinitis: A Mendelian Randomization Study. Cytokine, 177, Article ID: 156547. https://doi.org/10.1016/j.cyto.2024.156547
[38]
Li, L., Zhang, Y., Liu, H., Wang, T., Li, J. and Wang, X. (2023) Exploring Causal Relationships between Inflammatory Cytokines and Allergic Rhinitis, Chronic Rhinosinusitis, and Nasal Polyps: A Mendelian Randomization Study. FrontiersinImmunology, 14, Article ID: 1288517. https://doi.org/10.3389/fimmu.2023.1288517
[39]
Chen, Z., Suo, Y., Du, X. and Zhao, X. (2024) Genetically Predicted N-Methylhydroxyproline Levels Mediate the Association between Naive CD8+ T Cells and Allergic Rhinitis: A Mediation Mendelian Randomization Study. FrontiersinImmunology, 15, Article ID: 1396246. https://doi.org/10.3389/fimmu.2024.1396246
[40]
Xu, Z., Li, R., Wang, L., Wu, Y., Tian, Y., Su, Y., et al. (2024) Pathogenic Role of Different Phenotypes of Immune Cells in Airway Allergic Diseases: A Study Based on Mendelian Randomization. FrontiersinImmunology, 15, Article ID: 1349470. https://doi.org/10.3389/fimmu.2024.1349470
[41]
Tu, J., Wen, J., Luo, Q., Li, X., Wang, D. and Ye, J. (2024) Causal Relationships of Metabolites with Allergic Diseases: A Trans-Ethnic Mendelian Randomization Study. RespiratoryResearch, 25, Article No. 94. https://doi.org/10.1186/s12931-024-02720-6
[42]
Long, C.H., Wu, Z.C., Yang, B., et al. (2024) Micronutrients and Allergic Diseases: A Mendelian Randomization Study. InternationalArchivesofAllergyandImmunology, 1-11. https://doi.org/10.1159/000540376
