Exploring the genetic causal inference between plasma lipidome and hemorrhagic stroke.

Objectives: Recent research indicates that the plasma lipidome composition may undergo alterations following hemorrhagic stroke. Nevertheless, the causal inference between plasma lipidome and hemorrhagic stroke remains elusive.
Materials and Methods: Exposure data were achieved from a recent Genome-wide Association Study (GWAS) study of 179 lipid species involving 7174 individuals, while the outcome data were obtained from the FinnGen consortium (R10), including intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and non-traumatic intracranial hemorrhage (nITH). Two-sample bidirectional Mendelian randomization (MR) analyses were used to assess the causal inference between lipidome and hemorrhagic stroke, and inverse variance weighted served as the main method. Genetic correlations between lipidome and hemorrhagic stroke were assessed using linkage disequilibrium score regression (LDSC).
Results: After the false discovery rate (FDR) correction, Phosphatidylcholine (O-18:2_20:4) was identified as a substantial risk factor for ICH (OR,1.199; 95 % CI, 1.073-1.341; P _FDR = 0.073). Alternatively, Phosphatidylinositol (16:0_18:1) was a relevant protective factor (OR, 0.773; 95 % CI, 0.666-0.896; P _FDR = 0.069). Furthermore, the Sterol ester (27:1/20:3) (OR, 1.138; 95 % CI, 1.024-1.264; P _FDR = 0.086) was identified as the prominent risk factor for SAH. Finally, Sterol ester (27:1/20:4) (OR, 1.073; 95 % CI, 1.026-1.121; P _FDR = 0.030) and Phosphatidylinositol (16:0_18:1) levels (OR, 0.794; 95 % CI, 0.709-0.889; P _FDR = 0.007) was identified as risk and protective factors for nITH, respectively.
Conclusions: The causal relationship between plasma lipidome and hemorrhagic stroke is evident. Studying the plasma lipidome offers promising preventive strategies and potential therapeutic approaches for hemorrhagic stroke.
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.
(Copyright © 2025. Published by Elsevier Inc.)