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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
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Abstract:
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 =
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