分析231种饮食摄入与性早熟之间的因果关系——一项双样本孟德尔随机化研究

Analyzing the Causal Relationship between 231 Dietary Intake and Precocious Puberty —A Two-Sample Mendelian Randomization Study

目的:本文旨在将混杂因素的影响控制在最小的前提下,探讨特定的饮食摄入与性早熟(PP)发病的关系。方法:使用来自芬兰数据库(FinnGen)和英国生物样本库(UKB)的大规模全基因组关联研究(GWAS)汇总统计数据来探讨性早熟与231种饮食摄入之间的潜在关联。然后进行两样本孟德尔随机化(TSMR)分析,以进一步评估性早熟与饮食摄入之间的因果关系。结果:5种饮食摄入表现出正相关,即盐渍花生的摄入(ukb-b-1099) (OR = 1480.226, 95% CI = (14.460~151528.425), p = 0.002)、其他咸口小吃的摄入(ukb-b-18718) (OR = 326.312, 95% CI = (2.452~43431.149), p = 0.020)、西梅的摄入(ukb-b-3022) (OR = 1174.199, 95% CI = (6.603~208798.930), p = 0.007)、标准茶摄入量(ukb-b-3291) (OR = 1.011, 95% CI = (1.000~1.022), p = 0.040)及酒精摄入的频率(ukb-b-5799) (OR = 3.332, 95% CI = (1.491~7.448), p = 0.003);其余4种表现出负相关,即白鱼的摄入(ukb-b-5427) (OR = 0.004, 95% CI = (0.000~0.259), p = 0.010)、牛奶布丁的摄入(ukb-b-9857) (OR = 0.002, 95% CI = (0.000~0.297), p = 0.015)、煎饼的摄入(ukb-b-6500) (OR = 0.014, 95% CI = (0.000~0.808), p = 0.039)、平均每周摄入烈酒(ukb-b-1707) (OR = 0.039, 95% CI = (0.002~0.624), p = 0.022);此外,我们还发现性早熟与标准茶摄入量(ukb-b-3291) (OR = 0.402, 95% CI = (0.169~0.957), p = 0.04)、白鱼的摄入(ukb-b-5427) (OR = 0.998, 95% CI = (0.995~1.000), p = 0.038)存在反向因果关系。敏感性分析结果显示孟德尔随机化分析结果可靠。结论:盐渍花生、其他的咸口小吃、西梅、茶的摄入及酒精的摄入频率对性早熟存在致病效应;白鱼、牛奶布丁、煎饼的摄入及平均每周摄入烈酒与性早熟的延缓有关;患有性早熟可能会引起茶和白鱼的摄入量增加或减少。我们的研究结果为理解性早熟的发病机制提供了新的线索,重点关注会引起性早熟的饮食摄入,从而提供详细的饮食指导及干预,以期降低性早熟的发病率及年轻化趋势。Objective: This study aims to investigate the relationship between specific dietary intakes and the onset of precocious puberty (PP) while minimizing the influence of confounding factors. Methods: Summary statistics from large-scale Genome-Wide Association Studies (GWAS) from the Finnish database (FinnGen) and the UK Biobank (UKB) were utilized to explore potential associations between precocious puberty and 231 types of dietary intakes. Two-sampled Mendelian Randomization (TSMR) analysis was subsequently conducted to further assess the causal relationship between precocious puberty and dietary intakes. Results: Five dietary intakes showed positive correlations: intake of salted peanuts (ukb-b-1099) (OR = 1480.226, 95% CI = (14.460~151528.425), p = 0.002), intake of other salty snacks (ukb-b-18718) (OR = 326.312, 95% CI = (2.452~43431.149), p = 0.020), intake of prunes (ukb-b-3022) (OR = 1174.199, 95% CI = (6.603~208798.930), p = 0.007), standard tea intake (ukb-b-3291) (OR = 1.011, 95% CI = (1.000~1.022), p = 0.040), and frequency of alcohol intake (ukb-b-5799) (OR = 3.332, 95% CI = (1.491~7.448), p = 0.003). The remaining four showed negative correlations: intake of white fish (ukb-b-5427) (OR = 0.004, 95% CI = (0.000~0.259), p = 0.010), intake of milk pudding (ukb-b-9857) (OR = 0.002, 95% CI = (0.000~0.297), p = 0.015), intake of pancakes (ukb-b-6500) (OR = 0.014, 95% CI = (0.000~0.808), p = 0.039), and average weekly intake of spirits (ukb-b-1707) (OR = 0.039, 95% CI = (0.002~0.624), p = 0.022). Additionally, we found that precocious puberty has a reverse causal relationship with standard tea intake (ukb-b-3291) (OR = 0.402, 95% CI = (0.169~0.957), p = 0.04) and intake of white fish (ukb-b-5427) (OR = 0.998, 95% CI = (0.995~1.000), p = 0.038). Sensitivity analysis results indicated that the Mendelian Randomization analysis results were reliable. Conclusion: The intake of salted peanuts, other salty snacks, prunes, tea, and the frequency of alcohol intake have pathogenic effects on precocious puberty. The intake of white fish, milk pudding, pancakes, and the average weekly intake of spirits are associated with a delay in precocious puberty. Having precocious puberty may lead to increased or decreased intake of tea and white fish. Our findings provide new insights into understanding the pathogenesis of precocious puberty, focusing on dietary intakes that may induce precocious puberty, thereby offering detailed dietary guidance and interventions to reduce the incidence and youthful trend of precocious puberty.