Shared genetic architecture of psychiatric disorders and hemorrhoidal disease: a large-scale genome-wide cross-trait analysis

Zhangsendi Chen; Bowen Hu; Ji Sun; Yuhong Jiang; Zhe Chen; Chunmei Yang; Hongbo He; Weiguo Wang

doi:10.3389/fpsyt.2024.1456182

Shared genetic architecture of psychiatric disorders and hemorrhoidal disease: a large-scale genome-wide cross-trait analysis

Front Psychiatry. 2024 Nov 11:15:1456182. doi: 10.3389/fpsyt.2024.1456182. eCollection 2024.

Authors

Zhangsendi Chen¹, Bowen Hu¹, Ji Sun¹, Yuhong Jiang², Zhe Chen³, Chunmei Yang¹, Hongbo He¹, Weiguo Wang¹

Affiliations

¹ Division of Surgery, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
² Department of Integrated Traditional Chinese and Western Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
³ Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Abstract

Background: The genetic association between psychiatric disorders and hemorrhoidal disease (HEM) is still not well known. The work aims to investigate their comorbidity at a genetic level.

Methods: Utilizing recent large-scale genome-wide association studies (GWAS), we investigated the genetic overlap at the single nucleotide polymorphism (SNP), gene, and molecular level between depression and HEM, bipolar disorder (BD) and HEM, neuroticism and HEM, as well as schizophrenia (SCZ) and HEM. The cross-trait genes were validated through the utilization of transcriptome and proteome methodologies. The causal link was assessed using bidirectional two-sample Mendelian randomization analysis (MR) analysis. MRlap corrects for the potential bias in estimation caused by sample overlap.

Results: We discovered significant positive genetic associations between these four types of psychiatric disorders and HEM. Cross-phenotypic association analyses identified shared SNPs along with 17 specific loci between psychiatric disorders and HEM. MAGMA identified a total of 2304 pleiotropic genes, several of which showed significant expression in the results of transcriptome and proteome analyses. We observed that these genes are mostly associated with the regulation of transcription factors and particular DNA binding activities. Lastly, MR analysis provided evidence supporting a correlation between these conditions.

Conclusion: This study revealed a genetic correlation between four psychiatric disorders and HEM, identified pleiotropic loci, found multiple candidate genes, and confirmed causal relationships. This has enhanced our comprehension of the common genetic mechanisms of psychiatric disorders and HEM.

Keywords: Mendelian randomization; genetic overlap; hemorrhoidal disease; pleiotropic loci; psychiatric disorders.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The work was supported by grants from the Development Program of China (No. 2021YFC2009101), the National Natural Science Foundation of China (No. 81901462), the National Key Research and Development Program of China (No. 2021YFC2009103) and Fund for Health Care of Cadres in Sichuan Province (No. 2019-119).