The causal relationship between human blood metabolites and the risk of visceral obesity: a mendelian randomization analysis.
Lipids Health Dis
; 23(1): 39, 2024 Feb 07.
Article
de En
| MEDLINE
| ID: mdl-38326855
ABSTRACT
BACKGROUND:
We aimed to explore the causal relationship between blood metabolites and the risk of visceral obesity, as measured by visceral adipose tissue (VAT).METHODS:
Summary statistics for 486 blood metabolites and total, as well as sex-stratified, MRI-derived VAT measurements, adjusted for body mass index (BMI) and height, were collected from previous genome-wide association studies (GWAS). A two-sample Mendelian Randomization (MR) design was used. Comprehensive evaluation was further conducted, including sensitivity analysis, linkage disequilibrium score (LDSC) regression, Steiger test, and metabolic pathway analysis.RESULTS:
After multiple testing correction, arachidonate (204n6) has been implicated in VAT accumulation (ß = 0.35, 95%CI0.18-0.52, P < 0.001; FDR = 0.025). Additionally, several blood metabolites were identified as potentially having causal relationship (FDR < 0.10). Among them, lysine (ß = 0.67, 95%CI 0.28-1.06, P < 0.001; FDR = 0.074), proline (ß = 0.30, 95%CI0.13-0.48, P < 0.001; FDR = 0.082), valerate (ß = 0.50, 95%CI0.23-0.78, P < 0.001, FDR = 0.091) are associated with an increased risk of VAT accumulation. On the other hand, glycine (ß=-0.21, 95%CI -0.33-0.09), P < 0.001, FDR = 0.076) have a protective effect against VAT accumulation. Most blood metabolites showed consistent trends between different sexes. Multivariable MR analysis demonstrated the effect of genetically predicted arachidonate (204n6) and proline on VAT remained after accounting for BMI and glycated hemoglobin (HbA1c). There is no evidence of heterogeneity, pleiotropy, and reverse causality.CONCLUSION:
Our MR findings suggest that these metabolites may serve as biomarkers, as well as for future mechanistic exploration and drug target selection of visceral obesity.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Étude d'association pangénomique
/
Obésité abdominale
Type d'étude:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Humans
Langue:
En
Journal:
Lipids Health Dis
/
Lipids health dis. (Online)
/
Lipids in health and disease (Online)
Sujet du journal:
BIOQUIMICA
/
METABOLISMO
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Royaume-Uni