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Uterine leiomyoma (UL) is a common benign tumor among women of reproductive age. Alanine aminotransferase (ALT) is closely linked to metabolic and endocrine dysregulation, but its causal relationship with UL remains unclear. This study used Mendelian randomization (MR) to assess the potential causal association between ALT and UL.
Using summary statistics from genome-wide association studies (GWAS) of European ancestry, we performed two-sample MR to evaluate the causal effect of ALT on UL risk. We first conducted univariable MR and then performed multivariable MVMR analyses adjusting for body mass index (BMI), blood pressure, glycemic traits, lipid profiles, sex hormone-binding globulin (SHBG), and lifestyle-related factors to estimate the independent effect of ALT. Reverse MR (UL→ALT) was applied to assess directionality. Colocalization analyses were further performed to test whether ALT and UL share causal variants at key loci.
Univariable MR showed that genetically predicted higher ALT levels were associated with an increased risk of UL (OR=1.125, P=0.012; OR=1.143, P=0.007). In MVMR, the positive effect of ALT on UL remained robust after adjustment for multiple metabolic, hormonal, and lifestyle-related factors (OR=1.110-1.139; P=0.008-0.045). Reverse MR provided no evidence supporting a causal effect of UL on ALT. Colocalization analyses identified strong evidence of shared causal variants between ALT and UL at loci including HSPA4 and ATF1 (PP.H4>0.8).
This study provides multi-layered genetic evidence that elevated ALT independently increases the risk of UL, suggesting that hepatic metabolic dysfunction may contribute to UL development through pathways involving sex hormone metabolism and metabolic inflammation. As an easily accessible clinical marker, ALT may have potential value for risk prediction and early warning of UL.
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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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