Zheng Lingling, Liao Weiyao, Luo Shan, Li Bingyu, Liu Di, Yun Qingping, Zhao Ziyi, Zhao Jia, Rong Jianhui, Gong Zhiguo, Sha Feng, Tang Jinling
Department of Computational Biology and Medical Big Data, Shenzhen University of Advanced Technology, China.
Department of Computer Information Science, State Key Laboratory of Internet of Things for Smart City, University of Macau, Macau, China.
EClinicalMedicine. 2024 Sep 5;76:102810. doi: 10.1016/j.eclinm.2024.102810. eCollection 2024 Oct.
Previous conventional epidemiological studies found a J-shape relationship between alcohol consumption and dementia, but this result was subject to confounding biases and reverse causation. Therefore, we aimed to investigate the potential linear or non-linear causal association between alcohol consumption and the incident risk of dementia in current drinkers.
This study used data from the UK Biobank to investigate the relationship between alcohol consumption and dementia risk. 313,958 White British current drinkers, who were free of dementia during 2006-2010, were followed up until 2021. Alcohol consumption was self-reported and calculated according to the National Health Service guideline. The primary outcome was all-cause dementia identified through hospital and mortality records. We used multivariable Cox models with restricted cubic splines for conventional analysis and both non-linear and linear Mendelian Randomization (MR) analyses to assess causal relationships, employing a genetic score based on 95 SNPs identified from a meta-genome-wide association study of 941,280 people from Europe.
313,958 current drinkers consumed an average of 13.6 [IQR: 7.1-25.2] units/week alcohol (men averaged 20.2 [11.1-33.9] units/week and women 9.5 [5.3-16.7] units/week). During a mean follow-up of 13.2 years, 5394 (1.7%) developed dementia. Multivariable Cox model with restricted cubic spline functions identified a J-shaped relationship between alcohol consumption and dementia risk, with the lowest risk at 12.2 units/week. The non-linear MR failed to identify a significant non-linear causal relationship ( = 0.45). Both individual-level (HR: 2.22 95%CI [1.06-4.66]) and summary-level (1.89 [1.53-2.32]) linear MR analyses indicated that higher genetically predicted alcohol consumption increased dementia risk.
This study identified a positive linear causal relationship between alcohol consumption and dementia among current drinkers. The J-shaped association found in conventional epidemiological analysis was not supported by non-linear MR analyses. Our findings suggested that there was no safe level of alcohol consumption for dementia.
The Shenzhen Science and Technology Program and the Strategic Priority Research Program of Chinese Academy of Sciences.
以往的传统流行病学研究发现饮酒与痴呆症之间存在J形关系，但这一结果受到混杂偏倚和反向因果关系的影响。因此，我们旨在研究饮酒与当前饮酒者痴呆症发病风险之间潜在的线性或非线性因果关系。
本研究使用英国生物银行的数据来调查饮酒与痴呆症风险之间的关系。对2006年至2010年期间无痴呆症的313958名英国白人当前饮酒者进行随访，直至2021年。饮酒情况通过自我报告，并根据英国国家医疗服务体系指南进行计算。主要结局是通过医院和死亡记录确定的全因性痴呆症。我们使用带有受限立方样条的多变量Cox模型进行传统分析，以及非线性和线性孟德尔随机化（MR）分析来评估因果关系，采用基于从对941280名欧洲人进行的全基因组关联研究中鉴定出的95个单核苷酸多态性（SNP）的遗传评分。
313958名当前饮酒者平均每周饮酒13.6 [四分位间距：7.1 - 25.2] 单位（男性平均每周饮酒20.2 [11.1 - 33.9] 单位，女性为9.5 [5.3 - 16.7] 单位）。在平均13.2年的随访期间，5394人（1.7%）患上痴呆症。带有受限立方样条函数的多变量Cox模型确定饮酒与痴呆症风险之间存在J形关系每周饮酒12.2单位时风险最低。非线性MR未能识别出显著的非线性因果关系（P = 0.45）。个体水平（风险比：2.22，95%置信区间[1.06 - 4.66]）和汇总水平（1.89 [1.53 - 2.32]）的线性MR分析均表明较高的遗传预测饮酒量会增加痴呆症风险。
本研究确定了当前饮酒者中饮酒与痴呆症之间存在正线性因果关系。非线性MR分析不支持传统流行病学分析中发现的J形关联我们的研究结果表明不存在对痴呆症而言安全的饮酒水平。
深圳市科技计划和中国科学院战略性先导科技专项。
