The causal relationship between 179 lipid species and urolithiasis: a bidirectional and multivariable Mendelian...

Previous research has suggested a potential link between urolithiasis and lipid species levels. A Mendelian randomization (MR) study was conducted to investigate whether a causal relationship exists between genetic susceptibility to plasma lipids and the risk of urolithiasis.

Data on lipid species were collected from genome-wide association (GWAS) analyses of plasma lipidomes. For the initial analysis, GWAS data on urolithiasis were extracted using the GWAS ID ebi-a-GCST90018935. The inverse variance weighted (IVW) approach was utilized as the main method for MR analysis. Multivariable MR, multiple supplementary analyses, and comprehensive sensitivity analyses were also conducted. Additional independent datasets were utilized for replication analysis and meta-analysis.

Findings from the IVW method, repeated analyses, and meta-analysis revealed six significant causal effects of lipid species on urolithiasis. The specific lipid species identified were: phosphatidylcholine (PC; 16:1_20:4) levels [OR: 0.92; 95%CI: 0.87, 0.96; P = 6 × 10^- 4], PC (16:0_20:4) levels [OR: 0.94; 95%CI: 0.90, 0.98; P = 0.0017], phosphatidylethanolamine (PE; 18:2_0:0) levels [OR: 1.10; 95%CI: 1.04, 1.15; P = 4 × 10^- 4], PE (16:0_20:4) levels [OR: 1.05; 95%CI: 1.01, 1.09; P = 0.0028], PE (18:1_18:1) levels [OR: 1.06; 95%CI: 1.01, 1.11; P = 0.0136], and sterol ester (SE; 27:1/20:4) levels [OR: 0.93; 95%CI: 0.89, 0.96; P = 1.5 × 10^- 4].

The MR study proposes a potential causal link between six plasma lipids and urolithiasis. Particularly, SEs (27:1/20:4), PC (16:0_20:4), and PC (16:1_20:4) may serve as potential inhibitors of calcium-containing urolithiasis growth. The integration of genomics and lipidomics in MR analysis holds promise for early screening, prevention, and treatment of urinary tract stones.