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Association of childhood emotional neglect, circulating protein biomarkers, with gastrointestinal disorders among UK biobank participants

Journal of Affective Disorders, 2025

Qiao C., Qin X., Song Y., Guan R., Li B., Zuo Y., Wei W., Han T., Jiang W.

Disease areaApplication areaSample typeProducts
Other Diseases & Syndromes
Pathophysiology
Plasma
Olink Explore 3072/384

Olink Explore 3072/384

Abstract

Objective
To explore the association between CEN and GIDs, and elucidated the potential role of circulating protein biomarkers.
Patients and methods
The study utilized UK Biobank data from 156,686 participants, with data collection occurring between March 13, 2006 and October 1, 2010. Participants with GIDs at baseline were excluded from further analysis. CEN data were obtained from the baseline assessments. Differential protein analyses were conducted using OLINK data. GIDs and their subclasses were identified through electronic health records. Cox proportional hazards regression models were employed to assess the association between CEN and the risk of GIDs, along with sensitivity and multidimensional stratification analyses. Additionally, mediation analysis was performed to explore the role of differential protein biomarkers.
Results
The results indicated that the mild CEN (CENmild) group was associated with a significantly lower risk of various GIDs than the severe CEN (CENsevere) group, including overall GIDs (HR = 0.78,95%CI:0.74–0.81) and peptic ulcers (HR = 0.37,95%CI:0.20–0.68). OLINK differential analysis revealed that APOF expression was significantly higher in the CENmild group compared to the CENsevere group (PAPOF = 7.09E-08,FC = 0.048), whereas other differential protein expression (PBPIFB2 = 8.93E-06,FC = -0.122;PFABP4 = 3.19E-06,FC = -0.101;PGGH = 4.58E-07,FC = -0.054;PLEP = 5.39E-08,FC = -0.195) was significantly lower in the CENsevere group. Cox regression analysis showed that higher APOF expression was associated with a reduced risk of multiple GIDs, while the expression of other differential proteins increased the risk of corresponding GIDs. Mediation analysis indicated that these proteins mediated 0.5 % to 6.7 % of the CEN-GIDs association.
Conclusion
In this cohort study, CEN was significantly associated with a higher risk of GIDs in the adulthood, and circulating protein biomarkers partially mediated the associations.

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