湘雅医院：IBD与阿尔茨海默病的因果关联
- ①利用包含21982名AD患者及41944名对照的GWAS数据集获得AD的遗传关联因素；
- ②利用两项大规模GWAS数据集（共63197名IBD患者及83400名对照）获得IBD（包括CD和UC）的遗传关联因素；
- ③基于遗传因素预测的IBD与AD风险降低相关（OR=0.97），但可能受到严重的选择性生存偏差影响，而多变量MR分析显示UC及CD均与AD风险无显著关联；
- ④基于遗传因素预测的AD与UC风险降低相关（OR=0.91），与CD风险无显著关联。
主编推荐语
中南大学湘雅医院的郭纪锋团队Gut上发表的一篇Letter，应用多变量双向孟德尔随机化（MR）分析，研究IBD与阿尔茨海默病（AD）之间的关联，发现IBD与AD之间呈微弱的负向因果关联，但该关联可能受到选择性生存偏差、不准确的AD表型等因素影响。
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Association between inflammatory bowel disease and Alzheimer’s disease: multivariable and bidirectional Mendelian randomisation analyses
IBD与阿尔茨海默病的关联：多变量与双向孟德尔随机化分析
10.1136/gutjnl-2022-327860
2022-09-08, Short Article
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We read with interest the study by Zhang et al,1 showing that inflammatory bowel disease (IBD) was associated with increased risk of dementia, specifically Alzheimer’s disease (AD). Guo et al2 designed a Mendelian randomisation (MR) study to avoid potential confounding in observational studies, and demonstrated a genetically protective effect of IBD on AD, which is not in agreement with Zhang et al. However, some concerns in their MR study should be mentioned. First, the AD datasets from Kunkle et al3 include older clinically diagnosed patients (mean age: 71.1–82.6 years) and selection bias may be caused by selective survival from IBD and the competing risk of AD. That is, reduced life expectancy in patients with IBD may be accelerated by the presence of cardiovascular disease.4 Participants with IBD and dead from cardiovascular disease are not included into the AD genome-wide association study (GWAS), thus diminishing or reversing MR estimates for harmful exposures. Second, Guo et al2 used univariable MR to estimate causal roles of Ulcerative colitis (UC) and Crohn’s disease (CD) in AD, which may lead to horizontal pleiotropy due to a high degree of instrumental variable overlap between them.
First Authors:
Li Jiang
Correspondence Authors:
Ji-Feng Guo
All Authors:
Li Jiang,Jin-Chen Li,Lu Shen,Bei-Sha Tang,Ji-Feng Guo
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