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To explore whether there is any causal association between ketone bodies and cognitive performance employing the bidirectional and two-sample Mendelian randomization (MR) method.
Single nucleotide polymorphisms (SNPs) from the genome-wide association studies summary data from Europe were used as instrumental variables. The inverse-variance weighted method was used as the primary method to estimate the causal effect of ketone bodies instrumental variables with cognitive performance, and pathway and functional enrichment analyses were performed to predict potential mechanisms. Significance was ascertained with the use of Bonferroni-corrected significance thresholds (P=0.017).
Two-sample MR analysis showed that acetoacetate (β=0.075, 95% CI: 0.002-0.148, P=0.045) and β-hydroxybutyrate (β=0.082, 95% CI: 0.039-0.126, P=2.36×10-4) were causally associated with cognitive performance. However, the association of acetoacetate was no longer significant after Bonferroni-corrected. In addition, no link between acetone (β=0.041, 95% CI: -0.018-0.099, P=0.175) and cognitive performance was discovered. Pathway and functional enrichment analyses suggest that the mechanism of β-hydroxybutyrate effect on cognitive performance may be through a variety of ways, such as cholesterol metabolism and insulin resistance. In reverse MR Analysis, we found no causal effects of cognitive performance on ketone bodies.
Our findings support a causal relationship between β-hydroxybutyrate levels and better cognitive performance.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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