Association between inflammatory bowel disease and Alzheimer’s disease: multivariable and bidirectional Mendelian randomisation analyses
2022-09-08, Short Article
Abstract & Authors:展开
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.
Li Jiang,Jin-Chen Li,Lu Shen,Bei-Sha Tang,Ji-Feng Guo