Kidney stone disease and cardiovascular events: a study on bidirectional causality based on mendelian randomization

Yuanyuan Zhao; Yang Fan; Mengru Wang; Chenguang Yu; Mengchen Zhou; Dan Jiang; Dunfeng Du; Shanshan Chen; Xin Tu

doi:10.21037/tau-21-899

Kidney stone disease and cardiovascular events: a study on bidirectional causality based on mendelian randomization

Transl Androl Urol. 2021 Dec;10(12):4344-4352. doi: 10.21037/tau-21-899.

Authors

Yuanyuan Zhao^#^{1

2

3

4}, Yang Fan^#⁵, Mengru Wang⁶, Chenguang Yu⁶, Mengchen Zhou⁶, Dan Jiang⁶, Dunfeng Du^{1

2

3

4}, Shanshan Chen⁷, Xin Tu⁶

Affiliations

¹ Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.
³ NHC Key Laboratory of Organ Transplantation, Wuhan, China.
⁴ Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China.
⁵ Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁶ Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio‑X Institute, Huazhong University of Science and Technology, Wuhan, China.
⁷ Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

^# Contributed equally.

Abstract

Background: Kidney stone disease (KSD) has been reported to be associated with several cardiovascular diseases. However, the causality between the conditions remains unknown. In the study, we performed a study on bidirectional causality by two-sample Mendelian randomization (MR) to investigate the causality between KSD and cardiovascular diseases including coronary atherosclerosis, hypertension, and cardiomyopathy.

Methods: In the recent study, we performed a bidirectional two-sample MR study using available genome-wide association summary data from the online database MRBASE. We identified genetic variants associated with KSD in one European population from UK Biobank (version 2, n=462,933). Two phenotypes of samples were chosen from the population to define our genetic instrumental variables: (I) samples with the phenotype of kidney stone/ureter stone/bladder stone (ukb-b-8297), and (II) samples with the phenotype of kidney stone surgery/lithotripsy (ukb-b-13537). For cardiovascular diseases, we picked up another independent European population from FinnGen Biobank (n=93,421). We selected the exposure and outcome SNPs and then performed the two-sample MR using R package.

Results: After bidirectional causality by two-sample MR, we verified that genetic predisposition to KSD could increase the risk of coronary atherosclerosis (OR: 4.45×1037; SE=±7.80×10¹⁴, P for MR-Egger =0.024) and cardiomyopathy (OR: 5.35×10¹³; SE=±7.18×10⁶, P for IVW=0.045 for finn-a-I9_CARDMYO, and OR: 3.60×10²⁵; SE=±3.26×10¹², P for IVW=0.041 for finn-a-I9_CARDMYOOTH) when we used ukb-b-13537 as exposure group. Furthermore, hypertension could increase the risk of KSD (OR: 1.001; SE=±1.00, P for IVW=0.003) when we used ukb-b-8297 as exposure group, without detected pleiotropy bias (P>0.05).

Conclusions: We confirmed KSD may trigger causal pathological processes including coronary atherosclerosis and cardiomyopathy. Furthermore, hypertension may causally affect KSD.

Keywords: Kidney stone disease (KSD); bidirectional Mendelian randomization; cardiomyopathy; coronary atherosclerosis; hypertension.