Background: Bipolar disorder is a complex psychiatric condition with notable differences among its clinical subtypes including Type 1 and 2 disorders. Several studies have proposed that thyroid hormones may be involved in the etiology of bipolar disorders. Aims: This study employed a two-sample Mendelian Randomization (MR) approach to investigate the causal relationships between six thyroid hormone metrics (TSH, FT4, FT3, TT3, FT3/FT4, and TT3/FT4) and bipolar disorder, as well as Type 1 and 2 disorders, separately. Methods: We used GWAS summary statistics from the Thyroidomics Consortium (involving up to 271,040 individuals of European ancestry) to identify instruments for thyroid function metrics in MR analyses. Additionally, we included GWAS data for bipolar disorder, involving 41,917 cases and 371,549 controls of European ancestry, with 25,060 Type 1 and 6,781 Type 2 bipolar disorder cases. Results: We found that higher FT4 levels may have a protective causal effect against bipolar disorder and a suggestive causal effect on Type 1 bipolar disorder. In contrast, elevated FT3 levels and an increased FT3/FT4 ratio showed a suggestive harmful causal effect on Type 1 bipolar disorder. These associations remained robust across various MR methods, minimizing the likelihood of pleiotropy affecting our results. Conclusion: Our findings align with previous research but uniquely highlight the potentially harmful impact of elevated FT3 on Type 1 bipolar disorder. This study strengthens the evidence for FT4's role in bipolar disorder and highlights the need for further research into targeting thyroid hormone levels as a potential treatment strategy for Type 1 bipolar disorder.
Competing Interest StatementThe authors have declared no competing interest.
Funding StatementThis work was supported by the National Institute of General Medical Sciences of the National Institutes of Health (award number T32GM007281) and the Susan G. Komen Breast Cancer Foundation (TREND21675016 and SAC210203).
Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
All GWAS summary statistics utilized in this study are previously published and publicly available and for academic use without restriction. GWAS summary statistics for thyroid function utilized in this study are downloadable from the Thyroidomics Consortium at https://transfer.sysepi.medizin.uni-greifswald.de/thyroidomics/datasets/. GWAS summary statistics for bipolar disorders utilized in this study are downloadable from the Psychiatric Genomics Consortium at https://pgc.unc.edu/for-researchers/download-results/.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
Yes
Data AvailabilityCode for all analyses performed in this study are available at https://github.com/james-li-projects/MR_Thyroid_BPD.
留言 (0)