Fig. 1.

Conceptual framework of two-stage Mendelian randomization (MR) study. The study consists of a two-stage design that employs MR at all stages. First, we assessed the causality for the associations between 112 blood metabolites and the risk of breast cancer. Second, we investigated a broad spectrum of side effects associated with targeting identified metabolites in 679 non-breast cancer diseases. Among these, each disease belongs to one of 16 different International Classification of Disease (ICD)-9 chapters. At each stage, we adopted a Bonferroni-corrected P value threshold accounting for both the number of metabolites and diseases analyzed