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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. Multivariable MR (MVMR) is useful to …
Contributors LJ designed the study, undertook analyses, interpreted the results and wrote the first draft of the manuscript. LS, J-CL, B-ST and J-FG revised the manuscript.
Funding This study was supported by the national key plan for scientific research and development of China (2021YFC2501204), the Central Public-Interest Scientific Institution Basal Research Fund of Chinese Academy of Medical Sciences (Grant No.2018-12M-HL-025, Grant No.2019-RC-HL-025), the National Natural Science Foundation of China (Grant No.81873785, Grant No.82071439, Grant No. 81974202, Grant No.U20A20355), Technology Major Project of Hunan Provincial Science and Technology Department (Grant No.2021SK1010), Hunan Province Innovative Construction Project Science (Grant No.2019SK2335), the Innovation-driven Team Project from Central South University (Grant No.2020CX016), and the innovative team programme from Department of Science and Technology of Hunan Province (Grant No.2019RS1010).
Disclaimer The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.