Fig. 1.

Flowchart illustrating the systematic approach for identifying the association between antidiabetic drug targets and osteoarthritis phenotypes. This flowchart delineates the Mendelian Randomization framework used to assess the causal impact of antidiabetic drug targets on 12 osteoarthritis phenotypes identified from the largest osteoarthritis genome-wide association studies. If two neighbouring target genes shared the same IVs due to being located in the overlapped cis-region, these genes were combined and marked with a slash, as in “ABCC8/KCNJ11.” Abbreviations: OA, Osteoarthritis; MR, Mendelian randomisation; MVMR, multivariable Mendelian randomisation; SMR, summary-based Mendelian randomisation; IVs, instrumental variables; GWAS, genome-wide association studies; IVW, inverse variance weighted; T2DM, type 2 diabetes mellitus; HbA1c, haemoglobin A1C; FBG, fasting blood glucose; SNPs, single nucleotide polymorphisms; P_SMR, P-value for SMR analysis; P_HEIDI, P-value for heterogeneity in dependent instruments; eQTLs, expression quantitative trait loci; H0–H4, Hypotheses 0–4; PPA, posterior probability; THR, total hip replacement; TJR, total joint replacement; TKR, total knee replacement.