Disease clusters subsequent to anxiety and stress-related disorders and their genetic determinants

Xin Han, Qing Shen, Can Hou, Huazhen Yang, Wenwen Chen, Yu Zeng, Yuanyuan Qu, Chen Suo, Weimin Ye, Fang Fang, Unnur A. Valdimarsdóttir and Huan Song ()
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Xin Han: Sichuan University
Qing Shen: Tongji University School of Medicine
Can Hou: West China Hospital, Sichuan University
Huazhen Yang: West China Hospital, Sichuan University
Wenwen Chen: West China Hospital, Sichuan University
Yu Zeng: West China Hospital, Sichuan University
Yuanyuan Qu: West China Hospital, Sichuan University
Chen Suo: Fudan University
Weimin Ye: Karolinska Institutet
Fang Fang: Karolinska Institutet
Unnur A. Valdimarsdóttir: Karolinska Institutet
Huan Song: West China Hospital, Sichuan University

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Anxiety/stress-related disorders have been associated with multiple diseases, whereas a comprehensive assessment of the structure and interplay of subsequent associated diseases and their genetic underpinnings is lacking. Here, we first identify 136, out of 454 tested, medical conditions associated with incident anxiety/stress-related disorders attended in specialized care using a population-based cohort from the nationwide Swedish Patient Register, comprising 70,026 patients with anxiety/stress-related disorders and 1:10 birth year- and sex-matched unaffected individuals. By combining findings from the comorbidity network and disease trajectory analyses, we identify five robust disease clusters to be associated with a prior diagnosis of anxiety/stress-related disorders, featured by predominance of psychiatric disorders, eye diseases, ear diseases, cardiovascular diseases, and skin and genitourinary diseases. These five clusters and their featured diseases are largely validated in the UK Biobank. GWAS analyses based on the UK Biobank identify 3, 33, 40, 4, and 16 significantly independent single nucleotide polymorphisms for the link to the five disease clusters, respectively, which are mapped to several distinct risk genes and biological pathways. These findings motivate further mechanistic explorations and aid early risk assessment for cluster-based disease prevention among patients with newly diagnosed anxiety/stress-related disorders in specialized care.

Date: 2024
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DOI: 10.1038/s41467-024-45445-2

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