Causal Associations of Heparin-Binding Growth and Differentiation Factors With Thyroid Cancer: A Two-Sample Mendelian Randomization Study.

Background: Heparin-binding growth and differentiation factors (GDFs) play roles in various cellular processes and are potential contributors to thyroid cancer. Although population-based studies have documented associations between heparin-binding GDFs and thyroid cancer, their causal relationships remain unclear. Methods: A two-sample Mendelian randomization (MR) analysis was conducted using published genome-wide association studies (GWASs) data. The primary method for estimating causal effects was the inverse-variance weighted (IVW) approach, supplemented by multiple sensitivity analyses including weighted median, MR-Egger, and MR-PRESSO. Heterogeneity and outlier effects were systematically evaluated. Additionally, key MR findings were validated at the transcriptomic level using differential expression analysis of data from the Cancer Genome Atlas (TCGA). Results: The IVW method revealed significant causal relationships between midkine levels (OR = 1.2099, 95% CI: 1.013-1.445, Conclusions: Genetically predicted midkine levels and IGF2 were associated with thyroid cancer, and heparin-binding EGF-like growth factor was associated with malignant thyroid neoplasms. Future studies are needed to validate these findings.