Human blood metabolites and lacunar stroke: A Mendelian randomization study

Abstract

Background: Lacunar stroke accounts for a quarter of all strokes but little is known about the underlying pathological mechanisms. Analysis of serum metabolites may allow better understanding of the underlying biological processes. Mendelian randomization (MR) can provide information on the causality of associations. Aims: To identify causal relationships between serum metabolites and lacunar stroke. Methods: We applied a two-sample Mendelian randomization (MR) analysis to evaluate relationships between 486 serum metabolites and lacunar stroke. The inverse-variance weighted (IVW) method was used to estimate the causal relationship of the exposure on the outcome, while sensitivity analyses were performed using MR-Egger, weighted median and MR-PRESSO to eliminate the pleiotropy. We also performed a metabolic pathway analysis to identify potential metabolic pathways. Results: We identified 15 known (eight risk and seven protective) and 14 unknown serum metabolites associated with lacunar stroke. Among the known risk metabolites, two were lipids (1-linoleoylglycerophosphoethanolamine and dihomo-linolenate (20:3n3 or n6), five amino acids (kynurenine, isobutyrylcarnitine, aspartate, trans-4-hydroxyproline and 3-methyl-2-oxovalerate), and one a peptide (ADSGEGDFXAEGGGVR). The known protective metabolites included four lipids (4-androsten-3beta,17beta-diol disulfate 1, 1-palmitoleoylglycerophosphocholine, adrenate (22:4n6) and glycodeoxycholate), one amino acid (methionine) and two exogenous metabolites (homostachydrine and 2-methoxyacetaminophen sulphate). Metabolic pathway analysis identified several pathways that might be involved in the disease. Conclusion: We identified eight risk and seven protective human serum metabolites associated with lacunar stroke. Isobutyrylcarnitine was positively associated with an increased risk of lacunar stroke. In addition, 3-methyl-2-oxovalerate and aspartate may be involved in the disease pathogenesis through metabolic pathways.

Effects of immune cells on ischemic stroke and the mediating roles of metabolites

“…For MR analyses, the genetic variants utilized must be representative of the characteristics of IgD-D24-AC and 1 https://www.finngen.fi/en AA2S. Based on previous similar studies (49,50), we selected single nucleotide polymorphisms (SNPs) with p values less than (1 × 10 −5 ) as instrumental variables (IVs) to make them more informative. Furthermore, SNPs that exhibited a linkage disequilibrium (LD) coefficient (r 2 ) of less than 0.001 and those positioned more than 10,000 kilobases apart were chosen to ensure independence.…”

The causal relationship between serum metabolites and acne vulgaris: a Mendelian randomization study

“…Yi Feng et al have used MR to investigate the causal association of blood metabolites with lung cancer, breast cancer, ovarian cancer, and glioma, and identified 132 metabolites that may have a causal role in cancer progression 17 . Other MR studies have identified risk and protective serum metabolites associated with lacunar stroke 18 . MR provides a more convenient method for investigating the factors that influence disease.…”

The role of blood metabolites in oral cancer: insights from a Mendelian randomization approach

“…For the relationship between cancers and blood metabolomic, Guo et al. applied two-sample MR to identify blood metabolites associated with lacunar stroke, finding 15 known and 14 unknown metabolites with potential implications in disease pathogenesis ( 20 ). Liu et al.…”

“…Also, Chen et al identified a possible causal link between inflammatory bowel disease and oral cavity cancer (15). For the relationship between cancers and blood metabolomic, Guo et al applied two-sample MR to identify blood metabolites associated with lacunar stroke, finding 15 known and 14 unknown metabolites with potential implications in disease pathogenesis (20). Liu et al utilized bidirectional Mendelian randomization on Chinese individuals, revealing 58 causal relationships between the gut microbiome and blood metabolites, with a notable link between fecal Oscillibacter and Alistipes and decreased triglyceride concentration (21).…”