Association between human blood metabolome and the risk of hypertension

Dai, Nannan; Deng, Yujuan; Wang, Baishi

doi:10.1186/s12863-023-01180-z

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…However, no metabolites significantly correlated with SBP. In the MR analysis by Dai et al ( 62 ), 12 metabolites were significantly associated with DBP and 22 metabolites with SBP. Sensitivity analysis revealed that four metabolites, namely 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4)* (OR = 0.79, 95% CI: 0.70–0.88, P = 3.78 −05 ), behenoyl dihydrosphingomyelin [d18:0/22:0]* (OR = 1.84, 95% CI: 1.39–2.44, P = 2.04 −05 ), N-acetylarginine (OR = 1.15, 95% CI: 1.08–1.22, P = 1.17 −05 ), and N-acetylglutamine (OR = 1.15, 95% CI: 1.08–1.22, P = 1.17E −05 ), were significantly associated with DBP, and one metabolite, namely X-11381 (OR = 1.58, 95% CI: 1.28–1.94, P = 1.58 −05 ), was examined for its significant association with SBP.…”

Section: Discussionmentioning

confidence: 95%

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Causal association between blood metabolites and risk of hypertension: a Mendelian randomization study

Cheng,

Yun,

Fan

et al. 2024

Front. Cardiovasc. Med.

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BackgroundPrevious studies have indicated a strong link between blood metabolites and hypertension, however the causality of metabolites and hypertension is unknown.MethodsTwo-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between 486 blood metabolites and essential hypertension (EHT). Blood metabolite GWAS data was utilized as the exposure, with EHT GWAS data as the outcome. To further verify the results, another different source of EHT GWAS data was repeatedly analyzed. The major MR analytic approach used to determine causality was inverse variance weighted (IVW), with MR-Egger, Weighted Median, and MR-PRESSO models serving as supplements. We used the Cochran Q test to examine heterogeneity. Horizontal pleiotropy was examined using MR-Egger intercept and MR-PRESSO global test. The MR Steiger test confirmed the causal relationship between blood metabolites and EHT.ResultsIn this study, nine blood metabolites associated with EHT were preliminarily identified by MR analysis, including four known metabolites (N-acetylornithine, X-12510–2-aminooctanoic acid, creatine, hexadecanedioate) and five unknown metabolites. Then another source of EHT GWAS data was repeatedly analyzed for further verification, and two overlapped metabolites (N-acetylornithine, X-12510-2-aminooctanoic acid) were found. There was a negative correlation between N-acetylornithine and EHT (OR = 0.987, 95% CI = 0.980–0.993, P = 1.01 × 10−4), Cochran's Q test suggested there was no heterogeneity (Q = 31.7586, P = 0.1331), MR-Egger intercept and MR-PRESSO global test suggested there was no horizontal pleiotropy (P > 0.05), Leave-one-out analysis indicated that no single single-nucleotide polymorphism (SNP) had a significant effect on the results, and MR Steiger test confirmed that the direction of causality was correct (P < 0.001). There was a negative correlation between X-12510-2-aminooctanoic acid and EHT (OR = 0.982, 95% CI = 0.972–0.993, P = 0.0017), and there was no evidence of heterogeneity or pleiotropy in multiple sensitivity analyses.ConclusionThe study discovered some blood metabolites causally linked to EHT, which might lead to new understandings of the pathophysiology of hypertension.

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Section: Discussionmentioning

confidence: 95%

“…Previously, Qiao et al ( 61 ) and Dai et al ( 62 ) conducted MR analyses on blood metabolites and blood pressure, focusing on systolic blood pressure (SBP) and diastolic blood pressure (DBP). However, this study targets EHT, indicating a difference in study subjects.…”

Section: Discussionmentioning

confidence: 99%

Causal association between blood metabolites and risk of hypertension: a Mendelian randomization study

Cheng,

Yun,

Fan

et al. 2024

Front. Cardiovasc. Med.

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“…However, no metabolites significantly correlated with SBP. In the MR analysis by Dai et al (62), 12 metabolites were significantly associated with DBP and 22 metabolites with SBP. Sensitivity analysis revealed that four metabolites, namely 1-(1-enyl-stearoyl)-2arachidonoyl-GPE (P-18:0/20:4)* (OR = 0.79, 95% CI: 0.70-0.88, P = 3.78 −05 ), behenoyl dihydrosphingomyelin [d18:0/22:0]* (OR = 1.84, 95% CI: 1.39-2.44, P = 2.04 −05 ), N-acetylarginine (OR = 1.15, 95% CI: 1.08-1.22, P = 1.17 −05 ), and N-acetylglutamine (OR = 1.15, 95% CI: 1.08-1.22, P = 1.17E −05 ), were significantly associated with DBP, and one metabolite, namely X-11381 (OR = 1.58, 95% CI: 1.28-1.94, P = 1.58 −05 ), was examined for its significant association with SBP.…”

Section: Discussionmentioning

confidence: 95%

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Causal relationships between immunophenotypes, plasma metabolites, and temporomandibular disorders based on Mendelian randomization

Qiu,

Sun

2024

Sci Rep

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While numerous studies have underscored the implication of immune cells and metabolites in temporomandibular disorders (TMD), conclusive evidence for causality remains elusive. Consequently, our aim is to explore the causal connections between immunophenotypes and plasma metabolites in relation to TMD employing a bidirectional Mendelian randomization (MR) approach. Summary statistics data on 731 immunophenotypes (n = 3757) and 1091 plasma metabolites (n = 8299) were obtained from comprehensive genome-wide association studies (GWAS), while TMD data (5668 cases and 205,355 controls) were acquired from the FinnGen Consortium. Bidirectional MR analyses and a two-step MR approach assessed causal relationships and potential intermediaries. Various corrections and sensitivity analyses were utilized to assess the robustness of the findings. Two immunophenotypes and seven metabolites were significantly associated with TMD risk. Specifically, Alpha-hydroxyisovalerate mediated the link between CD33 on CD33dim HLA DR + CD11b + and TMD (β = 0.034, P = 5.95 × 10–5), while CD8 on NKT cells mediated the causal relationship between 5-acetylamino-6-formylamino-3-methyluracil levels and TMD (β = 0.069, P = 5.11 × 10–5). Our findings revealed the causal relationships between immunophenotypes and plasma metabolites on TMD from a genetic perspective, potentially aiding in TMD prevention.

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Association between human blood metabolome and the risk of hypertension

Cited by 4 publications

References 22 publications

Causal association between blood metabolites and risk of hypertension: a Mendelian randomization study

Causal association between blood metabolites and risk of hypertension: a Mendelian randomization study

Datasheet1.docx

Causal relationships between immunophenotypes, plasma metabolites, and temporomandibular disorders based on Mendelian randomization

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