Disease trajectory of high neuroticism and the relevance to psychiatric disorders: A retro‐prospective cohort study

Author:

Xia Ding12ORCID,Han Xin34ORCID,Zeng Yu34,Wang Jingru12,Xu Kelin256,Zhang Tiejun126,Jiang Yanfeng67ORCID,Chen Xingdong67ORCID,Song Huan348ORCID,Suo Chen126ORCID

Affiliation:

1. Department of Epidemiology, School of Public Health Fudan University Shanghai China

2. Ministry of Education Key Laboratory of Public Health Safety Fudan University Shanghai China

3. Mental Health Center and West China Biomedical Big Data Center, West China Hospital Sichuan University Chengdu China

4. Med‐X Center for Informatics Sichuan University Chengdu China

5. Department of Biostatistics School of Public Health Shanghai China

6. Taizhou Institute of Health Sciences Fudan University Taizhou China

7. State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences Fudan University Shanghai China

8. Center of Public Health Sciences, Faculty of Medicine University of Iceland Reykjavík Iceland

Abstract

AbstractBackgroundNeuroticism is a psychological personality trait that has a significant impact on public health and is also a potential predisposing factor for adverse disease outcomes; however, comprehensive studies of the subsequently developed conditions are lacking. The starting point of disease trajectory in terms of genetic variation remains unclear.MethodOur study included 344,609 adult participants from the UK Biobank cohort who were virtually followed up from January 1, 1997. Neuroticism levels were assessed using 12 items from the Eysenck Personality Questionnaire. We performed a phenome‐wide association analysis of neuroticism and subsequent diseases. Binomial tests and logistic regression models were used to test the temporal directionality and association between disease pairs to construct disease trajectories. We also investigated the association between polygenic risk scores (PRSs) for five psychiatric traits and high neuroticism.ResultsThe risk for 59 diseases was significantly associated with high neuroticism. Depression, anxiety, irritable bowel syndrome, migraine, spondylosis, and sleep disorders were the most likely to develop, with hazard ratios of 6.13, 3.66, 2.28, 1.74, 1.74, and 1.71, respectively. The disease trajectory network revealed two major disease clusters: cardiometabolic and chronic inflammatory diseases. Medium/high genetic risk groups stratified by the PRSs of four psychiatric traits were associated with an elevated risk of high neuroticism. We further identified eight complete phenotypic trajectory clusters of medium or high genetic risk for psychotic, anxiety‐, depression‐, and stress‐related disorders.ConclusionNeuroticism plays an important role in the development of somatic and mental disorders. The full picture of disease trajectories from the genetic risk of psychiatric traits and neuroticism in early life to a series of diseases later provides evidence for future research to explore the etiological mechanisms and precision management.

Funder

Science and Technology Commission of Shanghai Municipality

Shanghai Municipal Health Commission

West China Hospital, Sichuan University

National Key Research and Development Program of China

Publisher

Wiley

Subject

Psychiatry and Mental health

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