Causal relationship between neuroticism and functional gastrointestinal disorders: a Mendelian randomized study_Chinese Journal of Evidence-Based Medicine

Authors：

HUI xin ^1,2,3 , ZHENG Ya ^2,3 , WANG Yuping ^2,3 , ZHOU Yongning ^2,3 ,  GUO Qinghong ^2,3

1. The First Clinical Medical College, Lanzhou University, Lanzhou 730000, P. R. China;
2. Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China;
3. Gansu Province Clinical Research Center for Digestive Diseases, Lanzhou 730000, P. R. China;

Corresponding author：

GUO Qinghong, Email: gph@lzu.edu.cn

Keywords：

Neuroticism; Functional dyspepsia; Mendelian randomized analysis; Causality; Mediation analysis

DOI：

10.7507/1672-2531.202406062

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the relationship between neuroticism and functional gastrointestinal disorders using Mendelian randomized (MR). Methods Based on the genome-wide association study data of neuroticism and 2 functional gastrointestinal disorders, i.e., functional dyspepsia (FD), and irritable bowel syndrome (IBS), appropriate single nucleotide polymorphisms (SNP) were extracted as instrumental variables, and inverse variance weighted (IVW) was applied as the main analysis method, and sensitivity analyses were performed by Cochran’s Q test, MR-PRESSO test, MR-Egger intercept, and leave one out analysis. Further two-step MR analyses were performed to examine the mediating effects of coffee intake, alcohol consumption, smoking, depression. Results The univariable MR analysis showed that genetically determined neuroticism was positively causally associated with the risk of developing FD and IBS (FD: OR=1.448, 95%CI 1.057 to 1.983, P=0.021; IBS: OR=1.705, 95%CI 1.210 to 2.403, P=0.002). Cochran's Q-test, MR-Egger intercept, MR-PRESSO did not observe significant heterogeneity or horizontal pleiotropy. Leave-one-out analyses also did not find a large effect of individual SNPs on the overall results. Multivariable MR analyses showed that the association between neurotic personality and elevated risk of FD and IBS prevalence persisted even after adjusting for other confounders. Further two-step MR mediation analyses revealed that depression partially mediated this effect, with mediation proportions of 59.41% (95%CI 5.69% to 113.12%) and 67.53% (95%CI 31.55% to 103.51%), respectively. Conclusion There is a degree of causal association between neuroticism and FD and IBS, and depression may play an important mediating role in this association.

Citation： HUI xin, ZHENG Ya, WANG Yuping, ZHOU Yongning, GUO Qinghong. Causal relationship between neuroticism and functional gastrointestinal disorders: a Mendelian randomized study. Chinese Journal of Evidence-Based Medicine, 2025, 25(2): 155-161. doi: 10.7507/1672-2531.202406062 Copy

1.	Black CJ, Drossman DA, Talley NJ, et al. Functional gastrointestinal disorders: advances in understanding and management. Lancet, 2020, 396(10263): 1664-1674.
2.	Drossman DA, Hasler WL. Rome IV-functional GI disorders: disorders of gut-brain interaction. Gastroenterology, 2016, 150(6): 1257-1261.
3.	Van Oudenhove L, Levy RL, Crowell MD, et al. Biopsychosocial aspects of functional gastrointestinal disorders: how central and environmental processes contribute to the development and expression of functional gastrointestinal disorders. Gastroenterology, 2016, 150(6): 1355-1367.
4.	McAdams DP, Olson BD. Personality development: continuity and change over the life course. Annu Rev Psychol, 2010, 61: 517-542.
5.	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.
6.