Essential nutrients and cerebral small vessel diseases: a two-sample Mendelian randomization study.

Area of Science:

• Nutritional Neuroscience
• Genetic Epidemiology
• Cerebrovascular Health

Background:

• Cerebral small vessel disease (CSVD) is linked to nutrient intake, but causal relationships remain unclear.
• Previous research suggests potential associations between nutrients and CSVD, necessitating further investigation.
• Understanding these links is crucial for developing targeted prevention strategies for CSVD.

Purpose of the Study:

• To elucidate the causal associations between essential nutrients (amino acids, polyunsaturated fatty acids, minerals, vitamins) and acute CSVD manifestations (intracerebral hemorrhage, small vessel stroke).
• To employ a robust two-sample Mendelian randomization (MR) approach for assessing genetic links between nutrient levels and CSVD subtypes.
• To provide a genetic perspective on nutrient influences on CSVD risk.

Main Methods:

• Utilized large-scale European genome-wide association studies (GWASs) for CSVD cases and controls, alongside nutrient concentration GWAS data.
• Applied the inverse variance-weighted (IVW) method as the primary analysis for causality assessment.
• Conducted sensitivity analyses using simple median, weighted median, and MR-Egger methods to ensure result robustness.

Main Results:

• Elevated phenylalanine and dihomo-gamma-linolenic acid (DGLA) levels were associated with increased risk for intracerebral hemorrhage (ICH) or small vessel stroke (SVS).
• Docosapentaenoic acid (DPA), zinc, and arachidonic acid showed protective effects against ICH or SVS.
• Specific nutrient associations varied between CSVD subtypes, with phenylalanine and DGLA posing risks for nonlobar hemorrhage or SVS.

Conclusions:

• This study provides genetic evidence for the causal effects of specific nutrients on CSVD risk.
• Findings suggest potential for nutrient supplementation in CSVD prevention strategies.
• The research highlights the importance of considering nutrient status in managing cerebrovascular health.