Figure 1.

Schematic representation of the bidirectional 2SMR study. GM and CeD datasets were obtained from MiBioGen consortium and Immunochip study, respectively. GM dataset included genotype association of 211 taxa in 18,340 individuals; the CeD Immunochip was reanalyzed to only include genetic associations of HR-HLA individuals. Instrumental variables from exposure data were selected applying a p-value<10^-5 association threshold, a pairwise LD r²<0.001 and a 10,000 kb clumping window. The bidirectional 2SMR analysis: GM > HR-HLA CeD or HR-HLA CeD > GM was performed using five methods: Inverse Variance Weighted (IVW), MR Egger (MRE), Weighted Median (WMed), Weighted Mode (WMod), and Simple Mode (SMod).