Positive association between omega-3/6 polyunsaturated fatty acids and idiopathic normal pressure hydrocephalus: a mendelian randomization study.

Background

Idiopathic normal pressure hydrocephalus (iNPH) is a common disease among the elderly, which brings great harm to the health of patients and imposes a huge economic burden on the healthcare system. Research has shown that it is possible to prevent iNPH through nutritional and dietary interventions. Intake of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can reduce the risk of many diseases. In this study, we aimed to explore the association between omega-3/6 PUFAs and iNPH.

Methods

We conducted a two-sample Mendelian randomization (MR) study using summary data from publicly available genome-wide association studies (GWAS) to evaluate the potential impact of omega-3 and omega-6 PUFAs on the risk of iNPH in European populations. Inverse variance weighting was used as the main method for MR analysis, with Wald ratio, weighted median, MR-Egger, simple mode, and weighted mode as supplementary methods. In addition, we performed a series of instrument variable strength evaluations and sensitivity analyses to test the reliability of the study results. Finally, we also conducted a linkage disequilibrium score regression (LDSC) analysis to assess the genetic correlation and distinguish between causal associations and shared genetic variants between PUFAs and iNPH.

Results

One SD increase in genetically predicted levels of total omega-3 PUFAs (OR: 0.748; 95% CI: 0.597-0.937; p = 0.012; IVW), DHA (OR: 0.709; 95% CI: 0.532-0.945; p = 0.019; IVW), ALA (OR: 0.001; 95% CI: 1.17E-06-0.423; p = 0.026; Wald ratio), and DHA (OR: 0.709; 95% CI: 0.532-0.945; p = 0.019; IVW) were associated with a reduced iNPH risk. LDSC did not reveal any significant genetic correlations.

Conclusion

Higher genetically predicted levels of total omega-3 PUFAs, ALA, DHA, and DPA are associated with a reduced risk of iNPH. These findings have important implications for preventing iNPH and future nutritional guidance.