Li Chang-Lei, Liu Yu-Kun, Lan Ying-Ying, Wang Zu-Sen
Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China.
Department of Oncology Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266002, Shandong Province, China.
World J Clin Cases. 2024 Jul 16;12(20):4272-4288. doi: 10.12998/wjcc.v12.i20.4272.
Education, cognition, and intelligence are associated with cholelithiasis occurrence, yet which one has a prominent effect on cholelithiasis and which cardiometabolic risk factors mediate the causal relationship remain unelucidated.
To explore the causal associations between education, cognition, and intelligence and cholelithiasis, and the cardiometabolic risk factors that mediate the associations.
Applying genome-wide association study summary statistics of primarily European individuals, we utilized two-sample multivariable Mendelian randomization to estimate the independent effects of education, intelligence, and cognition on cholelithiasis and cholecystitis (FinnGen study, 37041 and 11632 patients, respectively; = 486484 participants) and performed two-step Mendelian randomization to evaluate 21 potential mediators and their mediating effects on the relationships between each exposure and cholelithiasis.
Inverse variance weighted Mendelian randomization results from the FinnGen consortium showed that genetically higher education, cognition, or intelligence were not independently associated with cholelithiasis and cholecystitis; when adjusted for cholelithiasis, higher education still presented an inverse effect on cholecystitis [odds ratio: 0.292 (95%CI: 0.171-0.501)], which could not be induced by cognition or intelligence. Five out of 21 cardiometabolic risk factors were perceived as mediators of the association between education and cholelithiasis, including body mass index (20.84%), body fat percentage (40.3%), waist circumference (44.4%), waist-to-hip ratio (32.9%), and time spent watching television (41.6%), while time spent watching television was also a mediator from cognition (20.4%) and intelligence to cholelithiasis (28.4%). All results were robust to sensitivity analyses.
Education, cognition, and intelligence all play crucial roles in the development of cholelithiasis, and several cardiometabolic mediators have been identified for prevention of cholelithiasis due to defects in each exposure.
教育、认知和智力与胆结石的发生有关，但哪一项对胆结石有显著影响，以及哪些心血管代谢危险因素介导了这种因果关系仍未阐明。
探讨教育、认知和智力与胆结石之间的因果关系，以及介导这些关系的心血管代谢危险因素。
应用主要为欧洲个体的全基因组关联研究汇总统计数据，我们利用两样本多变量孟德尔随机化方法来估计教育、智力和认知对胆结石和胆囊炎的独立影响（芬兰基因组研究，分别有37041例和11632例患者；n = 486484名参与者），并进行两步孟德尔随机化以评估21种潜在中介因素及其对每种暴露与胆结石之间关系的中介作用。
芬兰基因组联盟的逆方差加权孟德尔随机化结果显示，遗传上较高的教育水平、认知或智力与胆结石和胆囊炎无独立关联；在调整胆结石因素后，较高的教育水平对胆囊炎仍呈现反向影响[优势比：0.292（95%置信区间：0.171 - 0.501）]，这并非由认知或智力所导致。21种心血管代谢危险因素中有5种被视为教育与胆结石之间关联的中介因素，包括体重指数（20.84%）、体脂百分比（40.3%）、腰围（44.4%）、腰臀比（32.9%）和看电视时间（41.6%），而看电视时间也是从认知（20.4%）和智力到胆结石（28.4%）的中介因素。所有结果在敏感性分析中均稳健。
教育、认知和智力在胆结石的发生发展中均起关键作用，并且已确定了几种心血管代谢中介因素，可用于预防因每种暴露缺陷导致的胆结石。
