Potential Causal Association Between Plasma Lipidomes and Keloid: Analysis from a Two-Sample Mendelian Randomization

Keloid formation is a multifaceted biological response to skin injury characterized by fibrous connective tissue, and functional and aesthetic impairments. Recent research highlights the role of plasma lipidomes in various diseases, yet their specific relationship with keloid formation has not been extensively studied.

This study aims to elucidate the causal relationship between plasma lipidomes and keloid formation using a two-sample Mendelian randomization (MR) approach.

Firstly, we employed a two-sample MR framework, utilizing genetic instrumental variables (IVs) derived from large-scale genome-wide association studies (GWAS). The exposure data comprised 179 plasma lipid species measured in 7174 individuals of European ancestry, while outcome data on keloids were sourced from a GWAS involving 436,200 individuals. IVs were selected using a significance threshold of P < 1×10^-5 and linkage disequilibrium criteria, yielding 4507 independent single-nucleotide polymorphisms (SNPs). Causal effect estimates were calculated using multiple MR methods, and sensitivity analyses were conducted to evaluate the robustness of the findings.

The analysis suggested a significant association between elevated levels of Phosphatidylcholine (O-16:0_16:0) and increased risk of keloid formation (OR 1.399, 95% CI 1.166-1.678, p-value < 0.001) by Inverse-variance weighted (IVW). Sensitivity analyses confirmed the absence of heterogeneity and significant horizontal pleiotropy, reinforcing the validity of the causal inference.

Our findings indicate that specific lipid species, particularly Phosphatidylcholine, may be associated with an increased risk of keloid formation, highlighting a potential role of lipid metabolism in keloid pathophysiology.