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Causal relationship from heart failure to kidney function and CKD: A bidirectional two-sample mendelian randomization
Junyu Zhang1, Zhixi Hu1,2, Yuquan Tan1,2
1Institute of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China.
Insights
Genetic predisposition to Heart Failure (HF) increases the risk of Chronic Kidney Disease (CKD). This study used Mendelian Randomization to confirm a causal link, highlighting HF
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Genetic Epidemiology
Background:
- Heart Failure (HF) and Chronic Kidney Disease (CKD) are prevalent conditions with complex etiologies.
- Known risk factors for HF and CKD include hypertension, diabetes, and genetic factors, but precise causal links remain unclear.
- Mendelian Randomization (MR) utilizes genetic variants as instrumental variables to infer causality.
Purpose of the Study:
- To investigate the potential causal relationship between Heart Failure and Chronic Kidney Disease using a bidirectional Mendelian Randomization approach.
- To assess whether genetic predisposition to HF influences CKD risk, and vice versa.
Main Methods:
- A bidirectional two-sample Mendelian Randomization study was conducted using large-scale European genetic data.
- Data included over 47,000 HF cases and 51,000 CKD cases.
- Multiple MR methods (MR-Egger, IVW, WME) were employed for robust causal inference.
Main Results:
- A genetic predisposition for Heart Failure was significantly associated with an elevated risk of Chronic Kidney Disease (OR=1.12, p=0.009).
- This causal association remained significant after adjusting for diabetes and hypertension.
- No statistically significant causal link was observed from CKD to HF.
Conclusions:
- Heart Failure plays a significant causal role in the progression of Chronic Kidney Disease.
- Findings have implications for therapeutic strategies and the development of novel treatments for CKD.
- Further research across diverse populations is recommended to elucidate the HF-CKD relationship.
Background:
Heart Failure (HF) is a widespread condition that affects millions of people, and it is caused by issues with the heart and blood vessels. Even though we know hypertension, coronary artery disease, obesity, diabetes, and genetics can increase the risk of HF and Chronic Kidney Disease (CKD), the exact cause of these conditions remains a mystery. To bridge this gap, we adopted Mendelian Randomization (MR), which relies on genetic variants as proxies.
Methods:
We used data from European populations for our Bidirectional Two-Sample MR Study, which included 930,014 controls and 47,309 cases of HF from the HERMES consortium, as well as 736,396 controls and 51,256 cases of CKD. We also employed several MR variations, including MR-Egger, Inverse Variance Weighted (IVW), and Weighted Median Estimator (WME), to guarantee the results were accurate and comprehensive.).
Results:
In this study, the MR analysis found that individuals with a genetic predisposition for HF have an elevated risk of CKD. Our study revealed a significant association between the genetic prediction of HF and the risk of CKD, as evidenced by the IVW method [with an odds ratio (OR) of 1.12 (95% CI, 1.03-1.21), p = 0.009] and the WME [with an OR of 1.14 (95% CI, 1.03-1.26), p = 0.008]. This causal relationship remained robust even after conducting MR analysis while adjusting for the effects of diabetes and hypertension, yielding ORs of 1.13 (IVW:95% CI, 1.03-1.23), 1.12 (MR-Egger: 95% CI, 0.85-1.48), and 1.15 (WME:95% CI, 1.04-1.27) (p = 0.008). However, in the reverse analysis aiming to explore CKD and renal function as exposures and HF as the outcome, we did not observe a statistically significant causal link between CKD and HF.
Conclusion:
Our study demonstrates the significance of HF in CKD progression, thus having meaningful implications for treatment and the potential for discovering new therapies. To better understand the relationship between HF and CKD, we need to conduct research in a variety of populations.
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