Genetic evidence for the causal relationship between metabolic diseases and primary aldosteronism: insights from Mendelian randomization analysis.

PURPOSE: Although the relationship between metabolic diseases and primary aldosteronism has been recognized for years, the causal relationship between them remains unclear. Therefore, our study aimed to clarify this uncertainty.

METHODS

Mendelian randomization analysis was performed to explore potential causal links between metabolic diseases and primary aldosteronism. Next, we conducted a mediator analysis to explore the role of plasma proteins in the relationship between metabolic diseases and primary aldosteronism. Finally, phenome-wide association studies (Phe-WAS) were conducted to explore the relationship between primary aldosteronism and other diseases.

RESULTS

Genetically predicted some metabolic diseases are significantly causally associated with primary aldosteronism, including type 2 diabetes mellitus [odds ratio (OR): 1.20, 95% confidence interval (CI): 1.05-1.37, P = 8.65E-03), fasting insulin levels (OR: 13.66, 95% CI: 4.03-46.28, P = 2.66E-05), BMI (OR: 1.53, 95% CI: 1.09-2.15, P = 1.43E-02), waist-to-hip ratio (OR: 1.82, 95% CI: 1.08-3.06, P = 2.52E-02), waist circumference (OR: 1.77, 95% CI: 1.19-2.64, P = 4.79E-03), and alcohol consumption (OR: 25.82, 95% CI: 2.35-283.28, P = 7.80E-03). The mediator analysis showed that the mediating effect of waist-to-hip ratio via serine hydroxymethyltransferase 1 on primary aldosteronism accounted for 40% (OR: 1.27, 95% CI: 1.03-1.55, P = 2.20E-02). Finally, the Phe-WAS analysis showed that primary aldosteronism might increase the risk of cerebrovascular diseases.

CONCLUSION

This study provides genetic evidence suggesting that certain metabolic diseases may increase the risk of primary aldosteronism, highlighting the necessity of enhanced primary aldosteronism screening and prevention in patients with metabolic disorders.