ETA2023 45th Annual Meeting of the European Thyroid Association ETA 2023 Oral Session 8: Hypothyrodism / Nodules (5 abstracts)
Testing for a causal role of thyroid hormone measurements within the normal range: a systematic mendelian randomization study
Heba Alwan 1 , Jian’an Luan 2 , Alice Williamson 2 , Isobel Steward 2 , Nick Wareham 2 , Claudia Langenberg 2 & Maik Pietzner 2
1University of Bern, University of Cambridge, Switzerland; 2University of Cambridge
Background: Numerous observational studies suggested that variation in thyroid function parameters even within the normal range associates with adverse, in particular non-thyroidal, health outcomes, but causality for most remains to be established.
Methods: We combined individual level and summary level genetic prediction methods, i.e., polygenic scores and Mendelian randomization (MR), to systematically test for an association between liability to variations in thyrotropin (TSH) and free thyroxine (FT4) within the normal range and more than 6,000 molecular traits (metabolites and proteins) and 1,500 diseases across three large population-based cohorts. We replicated and expanded findings in a phenome-wide MR study in the OpenGWAS data base.
Results: We observed little evidence that genetic predisposition explaining variation in TSH and FT4 within the normal range to be associated with non-thyroidal traits across all data sets. Notable exceptions included associations between TSH and atrial fibrillation (odds ratio=0.92, adjusted p-value=3.61x10-2) as well as cardiometabolic biomarkers such as sex hormone binding globulin (β=-0.060, adjusted p-value=9.37x10-36) or total cholesterol (β=0.030, adjusted p-value=4.06x10-8), highlighting known pathways of thyroid hormone action.
Conclusion: Contrary to what has been shown in observational studies, we find little evidence of an association between genetically determined thyroid function within the normal range and non-thyroidal phenotypes, suggesting that previous findings suffered from confounding and that screening for thyroid function parameters in otherwise healthy adults is unlikely to have relevant public health impact.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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