Association of major depression, schizophrenia and bipolar disorder with thyroid cancer: a bidirectional two-sample Mendelian randomized study

Background: Major depression disease (MDD), schizophrenia (SCZ), and bipolar disorder (BD) are common psychiatric disorders and the relationship with thyroid cancer has been of great interest. This study aimed to investigate the potential causal effects of MDD, SCZ, BD, and thyroid cancer. Method: We used publicly available summary statistics from large-scale genome-wide association studies to select genetic variant loci associated with major depression disease (MDD), SCZ, BD, and thyroid cancer as instrumental variables (IVs), which were quality-controlled and clustered, and we used three Mendelian randomization (MR) methods: inverse variance weighted (IVW), MR-Egger regression and Weighted Median Estimator(WME) methods to estimate a bidirectional causal relationship between mental illness and thyroid cancer. In addition, we performed heterogeneity and multivariate tests to verify the validity of IVs. Result: We used a two-sample bidirectional MR analysis to find a positive causal association between MDD and thyroid cancer risk. The results of the IVW analysis (OR = 3.956 95% CI= 1.177-13.299; P = 0.026) and the WME method (OR = 5.563 95% CI= 0.998-31.008; P = 0.050) confirmed that MDD may increase the risk of thyroid cancer same conclusion. Additionally, our study found a correlation between genetic susceptibility to SCZ and thyroid cancer (OR = 1.532 95% CI= 1.123-2.088; P = 0.007). The results of the WME method analysis based on the median estimate (OR = 1.599 95% CI= 1.014-2.521; P = 0.043) also supported that SCZ may increase the risk of thyroid cancer. Furthermore, our study did not find a causal relationship between BD and thyroid cancer. In addition, the results of reverse MR analysis showed no significant causality between thyroid cancer and MDD, SCZ, and BD (P>0.05), ruling out the possibility of reverse causality. Conclusions: : This MR method analysis provides new evidence to support that MDD and SCZ may be positively associated with thyroid cancer risk, while also ruling out a correlation between BD and thyroid cancer. These results may have important implications for public health policy and clinical practice. Future studies will help elucidate this association's biological mechanisms and potential confounders.