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. 2023 Jun 22:10:1172587.
doi: 10.3389/fnut.2023.1172587. eCollection 2023.

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

Jiayi Li  1   2 , Kailin Xia  1 , Zhengrui Wang  1   2 , Yanru Liu  1   2 , Yicheng Tong  1   2 , Yuwei Wang  1   2 , Yumou Zhou  1   2 , Linjing Zhang  1   3   4 , Lu Tang  1   3   4 , Dongsheng Fan  1   3   4 , Qiong Yang  1
Affiliations

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

Jiayi Li et al. Front Nutr. .

Abstract

Background: Previous studies have suggested a potential association between nutrients and cerebral small vessel disease (CSVD), but this association has not been fully addressed.

Object: We intended to clarify the causal associations between four categories of essential nutrients (amino acids, polyunsaturated fatty acids, minerals and vitamins) and two acute manifestations of CSVD (intracerebral hemorrhage and small vessel stroke) using two-sample Mendelian randomization (MR) analysis.

Method: We obtained European-based large-scale genome-wide association studies (GWASs) related to CSVD (6,255 cases and 233,058 controls) and nutrient concentrations. Causality evaluation mainly included the results of the inverse variance-weighted (IVW) method. The simple median method, the weighted median method and the MR-Egger method were adopted for sensitivity analyses.

Results: For ICH or SVS, increased levels of phenylalanine (OR = 1.188, p < 0.001) and dihomo-gamma-linolenic acid (DGLA) (OR = 1.153, p = 0.001) showed risk effects, while docosapentaenoic acid (DPA) (OR = 0.501, p < 0.001), zinc (OR = 0.919, p < 0.001), and arachidonic acid (OR = 0.966, p = 0.007) showed protective effects. For lobar hemorrhage or SVS, AA (OR = 0.978, p < 0.001), zinc (OR = 0.918, p < 0.001), and retinol (OR = 0.753, p < 0.001) showed risk effects; DPA (OR = 0.682, p = 0.022), gamma-linolenic acid (OR = 0.120, p = 0.033) and 25(OH)D (OR = 0.874, p = 0.040) showed protective effects. For nonlobar hemorrhage or SVS, DGLA (OR = 1.088, p < 0.001) and phenylalanine (OR = 1.175, p = 0.001) showed risk effects.

Conclusion: Our study analyzed the effect of nutrients on CSVD risk from a genetic perspective, with implications for CSVD prevention through nutrient supplementation.

Keywords: Mendelian randomization; cerebral small vessel disease; intracerebral hemorrhage; nutrient; small vessel stroke.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The process of our MR analyses is shown in this flow chart. Three key assumptions for our two-sample MR study. Assumption 1: The selected instrumental variables (IVs) should be significantly related to nutrients. Assumption 2: The selected IVs are not associated with other confounders. Assumption 3: There is no independent causal pathway between IVs and the outcome other than through nutrients. IVs, instrumental variables; GWASs, genome-wide association studies; MR, Mendelian randomization; IVW, inverse variance-weighted; ICH, intracerebral hemorrhage; SVS, small vessel stroke; KB, kilo base.
Figure 2
Figure 2
Associations of amino acids and the risk of cerebral hemorrhage or SVS using the IVW method. For the image in the figure, the black diamond represents the OR value, the straight line represents 95% CI, and the dotted line represents OR = 1. IVW, inverse variance-weighted; OR, odds ratio; 95% CI, 95% confidence interval; ICH, intracerebral hemorrhage; SVS, small vessel stroke; SNPs, single nucleotide polymorphisms.
Figure 3
Figure 3
Associations of polyunsaturated fatty acids and the risk of cerebral hemorrhage or SVS using the IVW method. For the image in the figure, the black diamond represents the OR value, the straight line represents 95% CI, and the dotted line represents OR = 1. IVW, inverse variance-weighted; OR, odds ratio; 95% CI, 95% confidence interval; SVS, small vessel stroke; SNPs, single nucleotide polymorphisms.
Figure 4
Figure 4
Associations of minerals and the risk of cerebral hemorrhage or SVS using the IVW method. For the image in the figure, the black diamond represents the OR value, the straight line represents 95% CI, and the dotted line represents OR = 1. IVW, inverse variance-weighted; OR, odds ratio; 95% CI, 95% confidence interval; SVS, small vessel stroke; SNPs, single nucleotide polymorphisms.
Figure 5
Figure 5
Associations of vitamins and the risk of cerebral hemorrhage or SVS using the IVW method. For the image in the figure, the black diamond represents the OR value, the straight line represents 95% CI, and the dotted line represents OR = 1. IVW, inverse variance-weighted; OR, odds ratio; 95% CI, 95% confidence interval; SVS, small vessel stroke; SNPs, single nucleotide polymorphisms.
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