Full
Outline
To investigate the causal relationship between plasma arginine (Arg) levels and colorectal cancer (CRC) risk using a bidirectional two-sample mendelian randomization (MR) approach, thereby providing genetic evidence for this association.
Based on publicly available large-scale Genome-Wide Association Study (GWAS) data, bidirectional MR analysis was conducted with Arg and CRC. In the forward analysis, genetic variants associated with plasma Arg levels were used as instrumental variables to estimate their causal effect on CRC risk. The reverse analysis assessed the effect of genetic predisposition to CRC on Arg levels. The primary causal estimate, derived via the inverse-variance weighted (IVW) method, was supplemented by the weighted median (WM) and MR-Egger approaches for sensitivity analyses. Robustness was evaluated through heterogeneity tests (Cochran Q), assessments of horizontal pleiotropy (MR-Egger intercept), and leave-one-out sensitivity analyses.
The forward MR analysis revealed an inverse causal association between genetically predicted plasma Arg levels and CRC risk (OR=0.762, 95%CI: 0.589-0.986, P=0.039). Sensitivity analyses showed no significant heterogeneity (Cochran QP=0.222) or evidence of horizontal pleiotropy (MR-Egger intercept P=0.991). In the reverse direction, MR analysis found no significant causal effect of genetic liability for CRC on plasma Arg levels (P>0.05).
Genetically elevated plasma arginine levels are causally associated with a reduced risk of colorectal cancer, suggesting a potential protective role. No reverse causal relationship was found. This provides genetic evidence for further exploration of the potential role of arginine in the prevention or intervention of colorectal cancer.
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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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