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Randomized Controlled Trial
. 2024 Apr 9;24(1):261.
doi: 10.1186/s12888-024-05682-7.

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

Rongliang Qiu  1   2 , Huihui Lin  3 , Hongzhan Jiang  3 , Jiali Shen  3 , Jiaxi He  4 , Jinbo Fu  5   6
Affiliations
Randomized Controlled Trial

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

Rongliang Qiu et al. BMC Psychiatry. .

Abstract

Background: Major depressive disease (MDD), schizophrenia (SCZ), and bipolar disorder (BD) are common psychiatric disorders, and their 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.

Methods: We used publicly available summary statistics from large-scale genome-wide association studies to select genetic variant loci associated with MDD, SCZ, BD, and thyroid cancer as instrumental variables (IVs), which were quality controlled and clustered. Additionally, we used three Mendelian randomization (MR) methods, inverse variance weighted (IVW), MR-Egger regression and weighted median estimator (WME) methods, to estimate the bidirectional causal relationship between psychiatric disorders and thyroid cancer. In addition, we performed heterogeneity and multivariate tests to verify the validity of the IVs.

Results: We used two-sample bidirectional MR analysis to determine whether there was 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. Additionally, our study revealed 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 suggested that SCZ may increase the risk of thyroid cancer. Furthermore, our study did not find a causal relationship between BD and thyroid cancer incidence. In addition, the results of reverse MR analysis showed no significant causal relationships between thyroid cancer and MDD, SCZ, or BD (P > 0.05), ruling out the possibility of reverse causality.

Conclusions: This MR method analysis provides new evidence that MDD and SCZ may be positively associated with thyroid cancer risk while also revealing 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 the biological mechanisms of these associations and potential confounders.

Keywords: Bipolar disorder; Major depressive disease; Mendelian randomization; Schizophrenia; Thyroid cancer.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Flowchart of the design of a Mendelian randomized study of the causal association between psychiatric disorders and thyroid cancer. Blue solid lines represent associations between instrumental variables (SNPs) and exposure and between exposure and outcome. The red solid line represents reverse causality. psychiatric disorders include major depression, schizophrenia, and bipolar disorder
See this image and copyright information in PMC

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