Scholarlink

Introduction <p>Observational studies have increasingly acknowledged the influence of Phosphatidylinositol (PI) on metabolic syndrome (MetS). Nevertheless, the causal association between PI and MetS remains unclear due to the presence of confounding factors and the potential for reverse causation in observational settings. This study seeks to clarify the causal link between PI and MetS while investigating the role of mediating metabolites.</p> Methods <p>A two-sample Mendelian randomization (MR) analysis was performed to examine the association between PI and MetS, utilizing aggregated data from genome-wide association studies (GWAS). Additionally, a two-step MR approach was applied to quantify the mediation effect of metabolites on the PI-MetS relationship. The inverse variance weighted (IVW) method served as the primary analytical approach, complemented by various sensitivity analyses employing alternative techniques.</p> Results <p>A significant positive association was found between genetically predicted PI and a 17% increased risk of MetS. Genetically predicted metabolites, including 4-cholesten-3-one (IVW: OR 1.264, 95% CI 1.076–1.483, <i>p</i> = 0.004), N-acetylalliin (IVW: OR 1.189, 95% CI 1.008–1.402, <i>p</i> = 0.040), and the Adenosine 5’-diphosphate to 5-oxoproline ratio (IVW: OR 1.191, 95% CI 1.045–1.357, <i>p</i> = 0.009), were each significantly associated with an increased risks of MetS, accounting for 14.50, 11.41%, 11.87% and % of the total effect, respectively. Notably, the Retinol to oleoyl-linoleoyl-glycerol ratio (IVW: OR 0.643, 95% CI 0.466–0.887, <i>p</i> = 0.007) mediated 62.6% of the effect, highlighting its pivotal role in the causal pathway linking PI to MetS. Moreover, 1-palmitoyl-2-dihomo-linolenoyl-GPC (IVW: OR 0.865, 95% CI 0.752–0.995, <i>p</i> = 0.042) and the Creatine to carnitine ratio (IVW: OR 0.853, 95% CI 0.740–0.983, <i>p</i> = 0.028) were associated with a reduced risk of MetS, demonstrating inhibitory effects within their respective pathways that accounted to 35.03% and 8.45% reductions in risk, respectively.</p> Conclusions <p>Our MR analysis demonstrated a positive association between PI and an increased risk of MetS. Furthermore, the metabolite-mediated PI significantly influenced MetS risk. These findings may offer valuable insights into the pathogenesis of MetS and inform future clinical research.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Unraveling the causal pathway between phosphatidylinositol, metabolites, and metabolic syndrome: a Mendelian randomization study

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月20日

查看全文
  • YueGuang Yang,
  • YanLing Ma,
  • Ming Li,
  • YuBo Han,
  • Li Liu

摘要

Introduction

Observational studies have increasingly acknowledged the influence of Phosphatidylinositol (PI) on metabolic syndrome (MetS). Nevertheless, the causal association between PI and MetS remains unclear due to the presence of confounding factors and the potential for reverse causation in observational settings. This study seeks to clarify the causal link between PI and MetS while investigating the role of mediating metabolites.

Methods

A two-sample Mendelian randomization (MR) analysis was performed to examine the association between PI and MetS, utilizing aggregated data from genome-wide association studies (GWAS). Additionally, a two-step MR approach was applied to quantify the mediation effect of metabolites on the PI-MetS relationship. The inverse variance weighted (IVW) method served as the primary analytical approach, complemented by various sensitivity analyses employing alternative techniques.

Results

A significant positive association was found between genetically predicted PI and a 17% increased risk of MetS. Genetically predicted metabolites, including 4-cholesten-3-one (IVW: OR 1.264, 95% CI 1.076–1.483, p = 0.004), N-acetylalliin (IVW: OR 1.189, 95% CI 1.008–1.402, p = 0.040), and the Adenosine 5’-diphosphate to 5-oxoproline ratio (IVW: OR 1.191, 95% CI 1.045–1.357, p = 0.009), were each significantly associated with an increased risks of MetS, accounting for 14.50, 11.41%, 11.87% and % of the total effect, respectively. Notably, the Retinol to oleoyl-linoleoyl-glycerol ratio (IVW: OR 0.643, 95% CI 0.466–0.887, p = 0.007) mediated 62.6% of the effect, highlighting its pivotal role in the causal pathway linking PI to MetS. Moreover, 1-palmitoyl-2-dihomo-linolenoyl-GPC (IVW: OR 0.865, 95% CI 0.752–0.995, p = 0.042) and the Creatine to carnitine ratio (IVW: OR 0.853, 95% CI 0.740–0.983, p = 0.028) were associated with a reduced risk of MetS, demonstrating inhibitory effects within their respective pathways that accounted to 35.03% and 8.45% reductions in risk, respectively.

Conclusions

Our MR analysis demonstrated a positive association between PI and an increased risk of MetS. Furthermore, the metabolite-mediated PI significantly influenced MetS risk. These findings may offer valuable insights into the pathogenesis of MetS and inform future clinical research.