Causal relationship between liposome and essential hypertension based on two-sample Mendelian randomization analysis

doi:10.3969/j.issn.1674-8115.2026.03.008

Abstract

Abstract:

Objective ·A two-sample Mendelian randomization (TSMR) approach was employed to investigate the causal relationship between liposomes and essential hypertension. Methods ·Genome-wide association study (GWAS) data for essential hypertension were obtained from the FinnGen database, while lipid profile data were sourced from the European Bioinformatics Institute (EBI). Data on 179 liposomes were downloaded from the EBI GWAS database, and relevant single-nucleotide polymorphisms (SNPs) were screened as instrumental variables. Inverse-variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode methods, combined with sensitivity analysis, were employed to evaluate the causal associations between the 179 liposomes and essential hypertension. Results ·Eight types of liposomes were identified as being associated with essential hypertension. According to the IVW results, six types of liposomes significantly increased the risk of essential hypertension, including triglyceride (52:3) (OR=1.061, 95%CI 1.022‒1.101, P=0.002), phosphatidylinositol (16:0‒18:1) (OR=1.066, 95%CI 1.025‒1.107, P=0.001), triglyceride (50:2) (OR=1.086, 95%CI 1.036‒1.139, P<0.001), triglyceride (54:3) (OR=1.062, 95%CI 1.027‒1.099, P<0.001), triglyceride (50:1) (OR=1.098, 95%CI 1.045‒1.154, P<0.001), and triglyceride (52:2) (OR=1.071, 95%CI 1.035‒1.110, P<0.001). Two types of liposome reduced the risk of essential hypertension, including sphingomyelin (d40:2) (OR=0.968, 95%CI 0.937‒0.999, P=0.042) and phosphatidylcholine (O-16:1‒18:1) (OR=0.960, 95%CI 0.924‒0.998, P=0.038). The causal directions revealed by the other four methods were consistent with those of the IVW method. Cochran′s Q test revealed slight heterogeneity, but its impact on the robustness of the overall results was limited. MR-Egger regression indicated no evidence of horizontal pleiotropy. Leave-one-out cross-validation demonstrated high robustness of the results. Reverse MR analysis indicated that the onset of essential hypertension did not alter the type of the aforementioned liposomes. Conclusion ·There is a causal relationship between specific liposomes and essential hypertension. Triglycerides (52:3, 50:2, 54:3, 50:1, 52:2) and phosphatidylinositol (16:0‒18:1) are risk factors for essential hypertension, which may promote hypertension development through metabolic disturbances. Moreover, sphingomyelin (D40:2) and phosphatidylcholine (O-16:1‒18:1) may have protective effects against the occurrence of essential hypertension.

Key words: liposome, essential hypertension, Mendelian randomization (MR), causal relationship

CLC Number:

R544.1

Huang Xi, Hou Qinwu, Zhang Zhaowei, Wang Yanan, Yang Qinghui, Cheng Ling. Causal relationship between liposome and essential hypertension based on two-sample Mendelian randomization analysis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(3): 340-347.

Figures/Tables 4

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References 43

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Exposure factor	Variable	Pleiotropy			Heterogeneity
Exposure factor	Variable	Intercept	Standard error	P value	Method	Cochran Q	P value
Triglyceride (52:3)	Essential hypertension	0	0.006	0.942	IVW	103.532	<0.001
Phosphatidylinositl (16:0-18:1)	Essential hypertension	0.003	0.006	0.644	IVW	31.954	0.015
Triglyceride (50:2)	Essential hypertension	0.005	0.007	0.543	IVW	55.111	<0.001
Triglyceride (54:3)	Essential hypertension	0.004	0.005	0.418	IVW	82.530	<0.001
Triglyceride (50:1)	Essential hypertension	0.006	0.007	0.391	IVW	113.066	<0.001
Triglyceride (52:2)	Essential hypertension	0.004	0.006	0.470	IVW	53.829	<0.001
Sphingomyelin (d40:2)	Essential hypertension	-0.007	0.005	0.140	IVW	110.019	<0.001
Phosphatidylcholine (O-16:1-18:1)	Essential hypertension	0.001	0.007	0.887	IVW	5.067	<0.001

Exposure factor	Variable	Pleiotropy			Heterogeneity
Exposure factor	Variable	Intercept	Standard error	P value	Method	Cochran Q	P value
Triglyceride (52:3)	Essential hypertension	0	0.006	0.942	IVW	103.532	<0.001
Phosphatidylinositl (16:0-18:1)	Essential hypertension	0.003	0.006	0.644	IVW	31.954	0.015
Triglyceride (50:2)	Essential hypertension	0.005	0.007	0.543	IVW	55.111	<0.001
Triglyceride (54:3)	Essential hypertension	0.004	0.005	0.418	IVW	82.530	<0.001
Triglyceride (50:1)	Essential hypertension	0.006	0.007	0.391	IVW	113.066	<0.001
Triglyceride (52:2)	Essential hypertension	0.004	0.006	0.470	IVW	53.829	<0.001
Sphingomyelin (d40:2)	Essential hypertension	-0.007	0.005	0.140	IVW	110.019	<0.001
Phosphatidylcholine (O-16:1-18:1)	Essential hypertension	0.001	0.007	0.887	IVW	5.067	<0.001