Gut-Guo Jifeng research group used Mendelian randomization to explore the two-way causal relationship between inflammatory bowel disease and Alzheimer's disease

Written by—Jiang Li, Guo Jifeng

Editor—Summer Leaf

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset and progressive decline in memory and cognitive function as the main clinical manifestations
.
In recent years, the concept of the "gut-brain axis" has received great attention from the academic community, that is, there is a two-way information exchange between the intestine and the central nervous system, and more and more evidence shows that the dysfunction of the "gut-brain axis" is related to the occurrence of a variety of gastrointestinal diseases and central nervous system diseases [1].

。 In January 2021, Gut published a report by Zhang et al.
on inflammatory bowel disease ( Inflammatoryboweldisease (IBD) and dementia, the study used 1742 IBD patients in Taiwan to relate to A comparison of 17,420 control groups found that patients with IBD had a 2.
54-fold higher risk of dementia after diagnosis than those without IBD, including AD The risk is highest for two subtypes of IBD — ulcerative colitis (UC) and crohn's disease , CD) – increased risk of dementia with no clear difference [2].

However, since traditional observational studies are susceptible to residual confounders (caused by measurement errors and unknown confounders) and reverse causal bias, which can only suggest one correlation, causal inferences from these findings require further evaluation
.

Recently, the team of Professor Guo Jifeng of Xiangya Hospital of Central South University published a title in the international top journal "Gut" (IF: 31.
793).
Research paper "Association between inflammatory bowel disease and Alzheimer's disease: multivariable and bidirectional Mendelian randomisationanalyses.
"
。 The study explored IBD and its subtypes using the Mendelian randomization method (Mendelianrandomisatio n, MR).
UC and CD) and AD bidirectional causality
.
Professor Guo Jifeng of the Department of Neurology, Xiangya Hospital, Central South University, is the corresponding author of the paper, doctoral student Jiang Li is the first author of the paper, Professor Tang Beisha and Professor Shen Lu and Professor Li Jinchen of Xiangya Hospital of Central South University are important participating authors of the paper, and Xiangya Hospital of Central South University is the
first signature of the paper.
In this study, the authors found no strong evidence to support a causal relationship between IBD and its subtypes and AD, however, the authors found that AD may reduce UC New evidence of onset risk, further research based on this result will help reveal the pathogenesis of UC and may also provide new ideas
for drugs to treat UC.

The authors utilized published genome-wide association studies (GWAS) data related to IBD and its subtypes (UC and CD) and AD GWAS data, two-sample MR studies were carried out to explore the bidirectional causal relationship
between IBD, its subtypes and AD.
The GWAS data for IBD and its subtypes here come from Liu et al.
[3] and deLange, respectively the results of the GWAS study by et al.
[4]; Due to the late age of onset of AD, the GWAS dataset for AD typically includes older clinically diagnosed patients, and selective survival of IBD The competitive risk of AD may lead to selection bias, i.
e.
, the life expectancy of patients with IBD may be reduced by the onset of cardiovascular disease [5], and participants with IBD who die from cardiovascular disease may not be recruited In the GWAS study of AD, the MR estimates leading to harmful exposures may be weakened or even reversed to avoid the effect of selective survival bias on MR results, The authors used the GWAS dataset for clinical diagnosis of AD (21,982 patients and 41,944 controls) as the primary dataset[6] , another GWAS data based on AD surrogate cases (314278 cases) from the UK Biobank [7].
and data from a larger meta-analysis of GWAS in clinically diagnosed AD/AD surrogate cases (71,880 patients and 383378 controls).
[8] As a secondary dataset, participants in AD surrogate cases are less susceptible to selective survival bias due to their relatively young age
.
At the same time, due to the high degree of overlap of genetic instrumental variables between UC and CD, the authors used a multivariate MR approach to analyze UC and CD Independent causal effects
on AD.