A central limit theorem for the Euler method for SDEs with irregular drifts.

BACKGROUND

Retinal vessel caliber is strongly associated with systemic blood pressure (BP); however, the causal relationship between retinal vascular caliber and BP remains unclear. Understanding this relationship is essential for advancing predictive, preventive, and personalized medicine (PPPM) approaches to effectively manage hypertension and its related complications.

WORKING HYPOTHESIS: Microvessel morphology is causally related to blood pressure. By integrating genome-wide association studies, Mendelian randomization analysis, transcriptomic data, and multivariate genomic approaches, this study aims to identify predictive biomarkers, uncover preventive strategies, and develop personalized intervention targets, thereby advancing the principles of 3P medicine for improved cardiovascular health management.

METHODS AND

RESULTS

We conducted a comprehensive investigation into the genetic factors underlying retinal vessel calibers and their complex relationship with BP traits. Our genome-wide association study (GWAS) assess retinal vessel calibers-central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and the arteriole-to-venule ratio (AVR)-in a subset of 36,223 individuals of European descent from the UK Biobank. The analysis identified 9, 5, and 4 SNPs located in TNS, Y_RNA, PBLD, C10orf32-ASMT:AS3MT, GNB3:CDCA3, NTN4, COL4 A2, CTD-2378E21.1, WNT7B, VTA1, FCF1, NPLOC4, FUT1 and CSK region, which are significantly associated with CRAE, CRVE, and AVR, respectively. Genetic correlation analysis revealed shared heritability between BP traits and both CRAE and AVR, but not CRVE. Mendelian randomization analysis confirmed bidirectional causal relationships between CRAE and BP traits, whereas CRVE was neither influenced by nor influenced BP traits. To explore the potential regulatory mechanisms, we leveraged transcriptomic data and identified the following causal pathways in vessel tissue: The expression of MRPL23-AS1 and ULK3 was correlated with the elevation of blood pressure SBP and narrowing of the CRAE. Finally, we constructed a multivariable genetic model including CRAE, AVR, SBP, and DBP, suggesting a common driving factor which underlies these traits.

CONCLUSIONS

Our study elucidates the complex relationship between BP and retinal vessel caliber, highlighting potential intervention targets for lowering BP and vascular narrowing-related diseases. These findings contribute to the development of tailored prevention and treatment strategies aligned with PPPM principles.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-025-00411-w.