Evidence map›Paper›PMID 39191175›Full record

ArticleEBioMedicine2024

Testing for a causal role of thyroid hormone measurements within the normal range on human metabolism and diseases: a systematic Mendelian randomization.

Heba Alwan, Jian'an Luan, Alice Williamson, Julia Carrasco-Zanini, Isobel D Stewart, Nicholas J Wareham, Claudia Langenberg, Maik Pietzner

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Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Heba AlwanMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK; University of Bern, Institute of Primary Health Care (BIHAM), Bern, Switzerland; University of Bern, Graduate School for Health Sciences, Bern, Switzerland. Electronic address: heba.al-alwan@unibe.ch.
Jian'an LuanMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.
Alice WilliamsonMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK; Precision Healthcare University Research Institute, Queen Mary University of London, London, UK.
Julia Carrasco-ZaniniMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK; Precision Healthcare University Research Institute, Queen Mary University of London, London, UK.
Isobel D StewartMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.
Nicholas J WarehamMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.
Claudia LangenbergMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK; Precision Healthcare University Research Institute, Queen Mary University of London, London, UK; Computational Medicine, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
Maik PietznerMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK; Precision Healthcare University Research Institute, Queen Mary University of London, London, UK; Computational Medicine, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.

Funding

Medical Research Council MC_UU_12015/1
6 · The paper itself

Abstract

backgroundVariation in thyroid function parameters within the normal range has been observationally associated with adverse health outcomes. Whether those associations reflect causal effects is largely unknown.

methodsWe systematically tested associations between genetic differences in thyrotropin (TSH) and free thyroxine (FT4) within the normal range and more than 1100 diseases and more than 6000 molecular traits (metabolites and proteins) in three large population-based cohorts. This was performed by combining individual and summary level genetic data and using polygenic scores and Mendelian randomization (MR) methods. We performed a phenome-wide MR study in the OpenGWAS database covering thousands of complex phenotypes and diseases.

findingsGenetically predicted TSH or FT4 levels within the normal range were predominately associated with thyroid-related outcomes, like goitre. The few extra-thyroidal outcomes that were found to be associated with genetic liability towards high but normal TSH levels included atrial fibrillation (odds ratio = 0.92, p-value = 2.13 × 10

interpretationIn contrast to previous studies that have described the association with thyroid hormone levels and disease outcomes, our genetic approach finds little evidence of an association between genetic differences in thyroid function within the normal range and non-thyroidal phenotypes. The association described in previous studies may be explained by reverse causation and confounding.

fundingThis research was funded by the Swiss National Science Foundation (P1BEP3_200041). The Fenland study (DOI 10.22025/2017.10.101.00001) is funded by the Medical Research Council (MC_UU_12015/1, MC_PC_13046 and MC_UU_00006/1). The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1, MC-UU_12015/1, MC_PC_13048 and MC_UU_00006/1).

Indexed as

Mendelian Randomization AnalysisThyroid HormonesBiomarkersGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMultifactorial InheritancePhenotypePolymorphism, Single NucleotideThyroid DiseasesThyroid Function TestsThyrotropinThyroxineBiomarkersThyroid HormonesThyrotropinThyroxineHealth outcomesMendelian randomisationThyroid function

Identifiers

PMID39191175
PMCPMC11400601

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.