Fu Shuai, Li Qiang, Cheng Li, Wan Sheng, Wang Quan, Min Yonglong, Xie Yanghao, Liu Huizhen, Hu Taotao, Liu Hong, Chen Weidong, Zhang Yanmin, Xiong Fei
Department of Nephrology, Wuhan No. 1 Hospital, Wuhan, Hubei Province, People's Republic of China.
Int J Nephrol Renovasc Dis. 2025 Mar 7;18:71-85. doi: 10.2147/IJNRD.S511736. eCollection 2025.
The occurrence of urinary tract or kidney infection is correlated with intelligence, noncognitive education and cognition, but the causal relationship between them remains uncertain, and which risk factors mediate this causal relationship remains unknown.
The intelligence (n=269,867), noncognitive education (n=510,795) and cognition data (n=257,700) were obtained from genome-wide association studies (GWAS) conducted in individuals of European ethnicities. The genetic associations between these factors and urinary tract or kidney infection (UK Biobank, n=397,867) were analyzed using linkage disequilibrium score regression. We employed a two-sample univariate and multivariate Mendelian randomization to evaluate the causal relationship, and utilized a two-step Mendelian randomization to examine the involvement of 28 potential mediators and their respective mediating proportions.
The genetic correlation coefficients of intelligence, noncognitive education, cognition, and urinary tract or kidney infection were -0.338, -0.218, and -0.330. The Mendelian randomization using the inverse variance weighted method revealed each 1-SD increase in intelligence, the risk of infection decreased by 15.9%, while after adjusting for noncognitive education, the risk decreased by 20%. For each 1-SD increase in noncognitive education, the risk of infection decreased by 8%, which further reduced to 7.1% after adjusting for intelligence and to 6.7% after adjusting for cognition. For each 1-SD increase in cognition, the risk of infection decreased by 10.8%, increasing to 11.9% after adjusting for noncognitive education. The effects of intelligence and cognition are interdependent. 2 out of 28 potential mediating factors exhibited significant mediation effects in the causal relationship between noncognitive education and urinary tract or kidney infection, with body mass index accounting for 12.1% of the mediation effect and smoking initiation accounting for 14.7%.
Enhancing intelligence, noncognitive education, and cognition can mitigate the susceptibility to urinary tract or kidney infection. Noncognitive education exhibited independent effect, while body mass index and smoking initiation assuming a mediating role.
尿路感染或肾脏感染的发生与智力、非认知教育及认知相关,但其因果关系仍不明确,且介导这种因果关系的危险因素尚不清楚。
智力(n = 269,867)、非认知教育(n = 510,795)及认知数据(n = 257,700)来自对欧洲种族个体进行的全基因组关联研究(GWAS)。使用连锁不平衡评分回归分析这些因素与尿路感染或肾脏感染(英国生物银行,n = 397,867)之间的遗传关联。我们采用两样本单变量和多变量孟德尔随机化来评估因果关系,并利用两步孟德尔随机化来检验28个潜在中介因素的参与情况及其各自的中介比例。
智力、非认知教育、认知与尿路感染或肾脏感染的遗传相关系数分别为-0.338、-0.218和-0.330。使用逆方差加权法的孟德尔随机化显示,智力每增加1个标准差,感染风险降低15.9%,而在调整非认知教育因素后,风险降低20%。非认知教育每增加1个标准差,感染风险降低8%,在调整智力因素后进一步降至7.1%,在调整认知因素后降至6.7%。认知每增加1个标准差,感染风险降低10.8%,在调整非认知教育因素后增至11.9%。智力和认知的影响相互依存。28个潜在中介因素中有2个在非认知教育与尿路感染或肾脏感染的因果关系中表现出显著的中介作用,体重指数占中介作用的12.1%,开始吸烟占14.7%。
提高智力、非认知教育和认知水平可降低尿路感染或肾脏感染的易感性。非认知教育表现出独立作用,而体重指数和开始吸烟起中介作用。