The genetic associations of lipidome on bladder cancer: a Mendelian randomization study

Multiple epidemiological studies have demonstrated a correlation between the lipidome and bladder cancer (BC). Nonetheless, the current literature lacks consensus on the causal link between the lipidome and BC. We utilise a two-sample Mendelian randomisation approach to meticulously evaluate the causal link between the two variables.

A two-sample Mendelian randomisation (MR) analysis was performed utilising publically accessible genome-wide association research data. The principal technique utilised for the inquiry was the inverse variance-weighted (IVW) meta-analysis. Furthermore, Bayesian weighted Mendelian randomisation (BWMR) was employed to corroborate the findings. Supplementary validation was conducted utilising Cochran's Q test and methodologies including MR-Egger.

The two-sample MR analysis, in conjunction with BWMR analysis, revealed a correlation between the genetic prediction of the lipidome and the risk of BC. Sterol ester (SE) 27:1/16:0 (OR: 1.148, 95% CI: 1.020-1.293, p = 0.022), Sterol ester 27:1/20:3 (OR: 1.132, 95% CI: 1.006-1.274, p = 0.040), Phosphatidylcholine (PC) 18:0_20:3 (OR: 1.257, 95% CI: 1.101-1.436, p = 0.001), Sphingomyelin (SM) d38:1 (OR: 1.120, 95% CI: 1.016-1.235, p = 0.023), Sphingomyelin d40:2 (OR: 1.156, 95% CI: 1.033-1.295, p = 0.012), Triacylglycerol (TAG) 46:1 (OR: 1.178, 95% CI: 1.013-1.369, p = 0.034), Triacylglycerol 49:2 (OR: 1.219, 95% CI: 1.031-1.442, p = 0.021), Triacylglycerol 50:5 (OR: 1.173, 95% CI: 1.038-1.326, p = 0.011), and Triacylglycerol 52:6 (OR: 1.161, 95% CI: 1.007-1.339, p = 0.040) exhibited a positive correlation with an elevated risk of BC.

Genetic projections suggest a reciprocal causal link between the lipidome and BC, offering theoretical support and a basis for future clinical research.