Causal Relationship Between Intelligence, Noncognitive Education, Cognition and Urinary Tract or Kidney Infection: A Mendelian Randomization Study

Shuai Fu,* Qiang Li,* Li Cheng, Sheng Wan, Quan Wang, Yonglong Min, Yanghao Xie, Huizhen Liu, Taotao Hu, Hong Liu, Weidong Chen, Yanmin Zhang, Fei Xiong Department of Nephrology, Wuhan No. 1 Hospital, Wuhan, Hubei Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Xiong; Yanmin Zhang, Department of Nephrology, Wuhan No. 1 Hospital, No. 215 Zhongshan Avenue, Wuhan, Hubei Province, 430022, People’s Republic of China, Email [email protected]; [email protected]: 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.Methods: 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.Results: 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%.Conclusion: 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.Keywords: cognition, intelligence, kidney infection, mediation analyses, Mendelian randomization, noncognitive education, urinary tract infection