Causal Relationship Between Circulating Omega-3 Fatty Acid and Cerebral Small Vessel Disease: A Mendelian...

Area of Science:

• Neurology
• Genetics
• Nutritional Science

Background:

• Cerebral small vessel disease (CSVD) contributes to stroke and cognitive decline.
• Key CSVD markers include lacunar stroke (LS), white matter hyperintensity (WMH), white matter perivascular space (WMPVS), and cerebral microbleeds (CMB).
• The causal role of omega-3 fatty acids (FA) in CSVD pathogenesis is not well-established.

Purpose of the Study:

• To investigate the potential causal relationship between circulating omega-3 FA levels and distinct CSVD phenotypes.
• Utilizing Mendelian randomization (MR) to assess genetic associations with CSVD markers.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis.
• Instrumental variables (IVs) for omega-3 FA levels derived from a large genome-wide association study (GWAS) (N=115,060).
• CSVD phenotype data sourced from multiple large GWAS datasets for LS, WMH, CMB, and WMPVS.

Main Results:

• Elevated omega-3 FA levels showed a significant inverse association with cerebral microbleed (CMB) risk (IVW OR=0.82, 95% CI: 0.69-0.96).
• No significant causal associations were detected between omega-3 FA levels and WMH, WMPVS, or LS.
• Sensitivity analyses confirmed the robustness of findings, ruling out significant horizontal pleiotropy or reverse causality.

Conclusions:

• Higher circulating omega-3 FA levels are potentially causally linked to a reduced risk of cerebral microbleeds (CMB).
• Omega-3 FA may represent a modifiable factor for CMB prevention.
• Further research in diverse populations is warranted to confirm these findings.