Letter to the editor: Genetically determined IBD is associated with decreased risk of Alzheimer’s disease: a Mendelian randomisation study

We read with great interest the observation of eminent colleague Chen et al showing that patients with IBD had a higher incidence of dementia, particularly Alzheimer’s disease (AD, HR=6.19).1 Due to various confounding factors (age of onset, treatment, smoking, body mass index, etc), it is usually hard to evaluate the causal link between IBD and AD using observational studies. Two-sample Mendelian randomisation (MR) treated genetic variants as instrumental variables (IVs) for exposures, effectively minimising the impact of confounding factors. Using two-sample MR analysis, we adopt the publicly available summary statistics from large-scale genome-wide association studies (GWAS) to investigate the causal effect of IBD (Ncases=12 882; Ncontrols=21 770),2 including UC and Crohn’s disease (CD), on AD (Ncases=21 982, Ncontrols=41 944) of European descent.3 Briefly, single-nucleotide polymorphisms (SNPs) with p values less than 5E–08 for IBD were selected as IVs and were clumped based on the linkage disequilibrium (LD) structure (R2 <0.0001 within 10 000 kb, the 1000 Genomes Project European panel). In …