Identification of potential genetic Loci and polygenic risk model for Budd-Chiari syndrome in Chinese population

Xiaojun Hu; Xiaosen Jiang; Jia Li; Ni Zhao; Hairun Gan; Xinyan Hu; Luting Li; Xingtao Liu; Hong Shan; Yong Bai; Pengfei Pang

doi:10.1016/j.isci.2023.107287

Identification of potential genetic Loci and polygenic risk model for Budd-Chiari syndrome in Chinese population

iScience. 2023 Jul 11;26(8):107287. doi: 10.1016/j.isci.2023.107287. eCollection 2023 Aug 18.

Authors

Xiaojun Hu¹, Xiaosen Jiang^{2

3}, Jia Li^{4

5}, Ni Zhao¹, Hairun Gan¹, Xinyan Hu¹, Luting Li¹, Xingtao Liu⁶, Hong Shan¹, Yong Bai², Pengfei Pang^{1

7

8}

Affiliations

¹ Center for Interventional Medicine, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
² BGI-Shenzhen, Shenzhen, China.
³ College of Life Sciences, University of the Chinese Academy of Sciences, Beijing, China.
⁴ BGI Genomics, BGI-Shenzhen, Shenzhen, China.
⁵ Hebei Industrial Technology Research Institute of Genomics in Maternal & Child Health, Shijiazhuang BGI Genomics Co., Ltd, Shijiazhuang, China.
⁶ Changfeng Hospital of Jinjiang District, Chengdu, China.
⁷ Guangdong Provincial Key Laboratory of Biomedical Imaging, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
⁸ Guangdong Provincial Engineering Research Center of Molecular Imaging, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.

Abstract

Budd-Chiari syndrome (BCS) is characterized by hepatic venous outflow obstruction, posing life-threatening risks in severe cases. Reported risk factors include inherited and acquired hypercoagulable states or other predisposing factors. However, many patients have no identifiable etiology, and causes of BCS differ between the West and East. This study recruited 500 BCS patients and 696 normal individuals for whole-exome sequencing and developed a polygenic risk scoring (PRS) model using PLINK, LASSOSUM, BLUP, and BayesA methods. Risk factors for venous thromboembolism and vascular malformations were also assessed for BCS risk prediction. Ultimately, we discovered potential BCS risk mutations, such as rs1042331, and the optimal BayesA-generated PRS model presented an AUC >0.9 in the external replication cohort. This model provides particular insights into genetic risk differences between China and the West and suggests shared genetic risks among BCS, venous thromboembolism, and vascular malformations, offering different perspectives on BCS pathogenesis.

Keywords: Computational molecular modelling; Genetics; Genomics; Risk factor.