Shared genetic architecture and causal relationship between liver and heart disease

Ziyi Fang; Sixiang Jia; Xuanting Mou; Zhe Li; Tianli Hu; Yiting Tu; Jianqiang Zhao; Tianlong Zhang; Wenting Lin; Yile Lu; Chao Feng; Shudong Xia

doi:10.1016/j.isci.2024.109431

Shared genetic architecture and causal relationship between liver and heart disease

iScience. 2024 Mar 6;27(4):109431. doi: 10.1016/j.isci.2024.109431. eCollection 2024 Apr 19.

Authors

Ziyi Fang¹, Sixiang Jia², Xuanting Mou², Zhe Li², Tianli Hu², Yiting Tu³, Jianqiang Zhao², Tianlong Zhang⁴, Wenting Lin², Yile Lu², Chao Feng², Shudong Xia²

Affiliations

¹ Department of Gastroenterology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu 322000, China.
² Department of Cardiology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu 322000, China.
³ Department of Orthopedics, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁴ Department of Critical Care Medicine, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu 322000, China.

Abstract

This study investigates the relationship and genetic mechanisms of liver and heart diseases, focusing on the liver-heart axis (LHA) as a fundamental biological basis. Through genome-wide association study analysis, we explore shared genes and pathways related to LHA. Shared genetic factors are found in 8 out of 20 pairs, indicating genetic correlations. The analysis reveals 53 loci with pleiotropic effects, including 8 loci exhibiting shared causality across multiple traits. Based on SNP-p level tissue-specific multi-marker analysis of genomic annotation (MAGMA) analysis demonstrates significant enrichment of pleiotropy in liver and heart diseases within different cardiovascular tissues and female reproductive appendages. Gene-specific MAGMA analysis identifies 343 pleiotropic genes associated with various traits; these genes show tissue-specific enrichment primarily in the liver, cardiovascular system, and other tissues. Shared risk loci between immune cells and both liver and cardiovascular diseases are also discovered. Mendelian randomization analyses provide support for causal relationships among the investigated trait pairs.

Keywords: Bioinformatics; Genetics; Non-infectious disease.