Clustered Mendelian randomization analyses identify distinct and opposing pathways in the association between genetically influenced insulin-like growth factor-1 and type 2 diabetes mellitus.

Background: There is inconsistent evidence for the causal role of serum insulin-like growth factor-1 (IGF-1) concentration in the pathogenesis of human age-related diseases such as type 2 diabetes (T2D). Here, we investigated the association between IGF-1 and T2D using (clustered) Mendelian randomization (MR) analyses in the UK Biobank.

Methods: We conducted Cox proportional hazard analyses in 451 232 European-ancestry individuals of the UK Biobank (55.