The causal relationship between neuroticism and gastroesophageal reflux disease: A bidirectional Mendelian randomization study in the European population_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHOU Siding ¹ , XIAO Hongbi ¹ , GAO Mingjun ² , WANG Mengmeng ² , WANG Xiaolin ³ ,  SHU Yusheng ³

1. Department of Medical College, Yangzhou University, Yangzhou, 225000, Jiangsu, P. R. China;
2. Department of Dalian Medical University, Dalian, 116000, Liaoning, P. R. China;
3. Department of Thoracic Surgery, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, 225000, Jiangsu, P. R. China;

Corresponding author：

SHU Yusheng, Email: 18051061999@yzu.edu.cn

Keywords：

Neuroticism; gastroesophageal reflux disease; causal relationship; Mendelian randomization

DOI：

10.7507/1007-4848.202309044

Video：

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Objective To analyze the relationship between neuroticism and gastroesophageal reflux disease (GERD) using the Mendelian randomization (MR) method. Methods Exposure and outcome data were downloaded from the Integrative Epidemiology Unit (IEU) database in August 2023, including summary statistics from genome-wide association studies (GWAS) for neuroticism (n=374 323) and GERD (n=602 604). MR was conducted using the weighted median method, MR-Egger method, inverse variance weighted method, weighted mode method, and simple mode method. The causal relationship between the two was assessed using odds ratio (OR), and sensitivity analyses were performed to ensure the accuracy of the results. Results Neuroticism was associated with an increased risk of GERD [OR=1.229, 95%CI (1.186, 1.274), P<0.001]. Similarly, GERD was associated with an increased risk of neuroticism [OR=1.786, 95%CI (1.623, 1.965), P<0.001]. Conclusion There is a bidirectional causal relationship between neuroticism and gastroesophageal reflux disease.

Citation： ZHOU Siding, XIAO Hongbi, GAO Mingjun, WANG Mengmeng, WANG Xiaolin, SHU Yusheng. The causal relationship between neuroticism and gastroesophageal reflux disease: A bidirectional Mendelian randomization study in the European population. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2025, 32(6): 814-818. doi: 10.7507/1007-4848.202309044 Copy

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12.	Duckworth A, Gibbons MA, Allen RJ, et al. Telomere length and risk of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease: A mendelian randomisation study. Lancet Respir Med, 2021, 9(3): 285-294.
13.	Huang D, Lin S, He J, et al. Association between COVID-19 and telomere length: A bidirectional Mendelian randomization study. J Med Virol, 2022, 94(11): 5345-5353.
14.	Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: A review. Res Synth Methods, 2019, 10(4): 486-496.
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16.	Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA, 2017, 318(19): 1925-1926.
17.	Xiang K, Wang P, Xu Z, et al. Causal effects of gut microbiome on systemic lupus erythematosus: A two-sample mendelian randomization study. Front Immunol, 2021, 12: 667097.
18.	Burgess S, Thompson SG. Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol, 2011, 40(3): 755-764.
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20.	Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol, 2017, 46(6): 1985-1998.
21.	Hemani G, Zheng J, Elsworth B, et al. The MR-base platform supports systematic causal inference across the human phenome. Elife, 2018, 7: e34408.
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23.	Lee YC, Wang HP, Chiu HM, et al. Comparative analysis between psychological and endoscopic profiles in patients with gastroesophageal reflux disease: A prospective study based on screening endoscopy. J Gastroenterol Hepatol, 2006, 21(5): 798-804.

1. Lin J, Li L, Pan N, et al. Neural correlates of neuroticism: A coordinate-based meta-analysis of resting-state functional brain imaging studies. Neurosci Biobehav Rev, 2023, 146: 105055.
2. Terracciano A, Aschwanden D, Stephan Y, et al. Neuroticism and risk of Parkinson's disease: A meta-analysis. Mov Disord, 2021, 36(8): 1863-1870.
3. Xia C, Pickett SJ, Liewald DCM, et al. The contributions of mitochondrial and nuclear mitochondrial genetic variation to neuroticism. Nat Commun, 2023, 14(1): 3146.
4. Terracciano A, Aschwanden D, Passamonti L, et al. Is neuroticism differentially associated with risk of Alzheimer's disease, vascular dementia, and frontotemporal dementia? J Psychiatr Res, 2021, 138: 34-40.
5. Goodwin RD, Cox BJ, Clara I. Neuroticism and physical disorders among adults in the community: Results from the National Comorbidity Survey. J Behav Med, 2006, 29(3): 229-238.
6. Almas A, Moller J, Iqbal R, et al. Effect of neuroticism on risk of cardiovascular disease in depressed persons: A Swedish population-based cohort study. BMC Cardiovasc Disord, 2017, 17(1): 185.
7. Richter JE, Rubenstein JH. Presentation and epidemiology of gastroesophageal reflux disease. Gastroenterology, 2018, 154(2): 267-276.
8. Katzka DA, Kahrilas PJ. Advances in the diagnosis and management of gastroesophageal reflux disease. BMJ, 2020, 371: m3786.
9. Zeng Y, Cao S, Yang H. The causal role of gastroesophageal reflux disease in anxiety disorders and depression: A bidirectional Mendelian randomization study. Front Psychiatry, 2023, 14: 1135923.
10. Miao Y, Yuan S, Li Y, et al. Bidirectional association between major depressive disorder and gastroesophageal reflux disease: Mendelian randomization study. Genes (Basel), 2022, 13(11): 2010.
11. Jones HJ, Borges MC, Carnegie R, et al. Associations between plasma fatty acid concentrations and schizophrenia: A two-sample Mendelian randomisation study. Lancet Psychiatry, 2021, 8(12): 1062-1070.
12. Duckworth A, Gibbons MA, Allen RJ, et al. Telomere length and risk of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease: A mendelian randomisation study. Lancet Respir Med, 2021, 9(3): 285-294.
13. Huang D, Lin S, He J, et al. Association between COVID-19 and telomere length: A bidirectional Mendelian randomization study. J Med Virol, 2022, 94(11): 5345-5353.
14. Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: A review. Res Synth Methods, 2019, 10(4): 486-496.
15. Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ, 2018, 362: k601.
16. Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA, 2017, 318(19): 1925-1926.
17. Xiang K, Wang P, Xu Z, et al. Causal effects of gut microbiome on systemic lupus erythematosus: A two-sample mendelian randomization study. Front Immunol, 2021, 12: 667097.
18. Burgess S, Thompson SG. Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol, 2011, 40(3): 755-764.
19. Burgess S, Thompson SG. Bias in causal estimates from Mendelian randomization studies with weak instruments. Stat Med, 2011, 30(11): 1312-1323.
20. Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol, 2017, 46(6): 1985-1998.
21. Hemani G, Zheng J, Elsworth B, et al. The MR-base platform supports systematic causal inference across the human phenome. Elife, 2018, 7: e34408.
22. Brew BK, Almqvist C, Lundholm C, et al. Comorbidity of atopic diseases and gastro-oesophageal reflux: Evidence of a shared cause. Clin Exp Allergy, 2022, 52(7): 868-877.
23. Lee YC, Wang HP, Chiu HM, et al. Comparative analysis between psychological and endoscopic profiles in patients with gastroesophageal reflux disease: A prospective study based on screening endoscopy. J Gastroenterol Hepatol, 2006, 21(5): 798-804.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

The causal relationship between neuroticism and gastroesophageal reflux disease: A bidirectional Mendelian randomization study in the European population

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