Yeung Chris Ho Ching, Au Yeung Shiu Lun, Schooling C Mary
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
J Psychiatr Res. 2022 Nov;155:550-558. doi: 10.1016/j.jpsychires.2022.09.052. Epub 2022 Sep 29.
Alzheimer's disease may have an autoimmune component, but the association is unclear.
The objective of this Mendelian randomization (MR) study was to evaluate the association of liability to autoimmune diseases with Alzheimer's disease.
A systematic search was done using PubMed to identify autoimmune diseases that have been suggested as associated with Alzheimer's disease. Genetic predictors of these autoimmune diseases were obtained from the largest and most recent genome-wide association studies (GWAS). Genetic associations with clinically-diagnosed Alzheimer's disease were obtained from the International Genomics of Alzheimer's Project GWAS (21982 cases; 41944 controls); and with parental and sibling history of Alzheimer's disease from the UK Biobank GWAS (27696 maternal, 14338 paternal and 2171 sibling cases). MR estimates were obtained using inverse variance weighting, MR-Egger and weighted median. To address possible selection bias due to inevitably recruiting only survivors, the analysis was repeated in younger people, i.e., UK Biobank siblings and adjusting for competing risk of Alzheimer's disease.
Of the 7 autoimmune diseases considered, liability to psoriasis and sarcoidosis were not associated with Alzheimer's disease. Some evidence was found for liability to multiple sclerosis being associated with higher risk and liability to Sjogren's syndrome with lower risk of Alzheimer's disease. Associations found for liability to giant cell arteritis, type 1 diabetes and rheumatoid arthritis were inconsistent in sensitivity analyses.
Liability to multiple sclerosis and Sjogren's syndrome could be associated with Alzheimer's disease. The underlying mechanisms, such as the role of myelin and neuroinflammation, should be further investigated.
阿尔茨海默病可能存在自身免疫成分，但两者之间的关联尚不清楚。
本孟德尔随机化（MR）研究旨在评估自身免疫性疾病易感性与阿尔茨海默病之间的关联。
使用PubMed进行系统检索，以确定已被认为与阿尔茨海默病相关的自身免疫性疾病。这些自身免疫性疾病的遗传预测因子来自最大且最新的全基因组关联研究（GWAS）。与临床诊断的阿尔茨海默病的遗传关联来自国际阿尔茨海默病基因组计划GWAS（21982例病例；41944例对照）；与阿尔茨海默病的父母和兄弟姐妹病史的遗传关联来自英国生物银行GWAS（27696例母亲、14338例父亲和2171例兄弟姐妹病例）。使用逆方差加权、MR-Egger和加权中位数获得MR估计值。为解决因不可避免地仅招募幸存者而可能产生的选择偏倚，在年轻人（即英国生物银行的兄弟姐妹）中重复分析，并对阿尔茨海默病的竞争风险进行调整。
在所考虑的7种自身免疫性疾病中，银屑病和结节病的易感性与阿尔茨海默病无关。发现一些证据表明，多发性硬化症易感性与阿尔茨海默病风险较高相关，干燥综合征易感性与阿尔茨海默病风险较低相关。在敏感性分析中，巨细胞动脉炎、1型糖尿病和类风湿关节炎易感性的关联不一致。
多发性硬化症和干燥综合征易感性可能与阿尔茨海默病相关。应进一步研究其潜在机制，如髓鞘和神经炎症的作用。
