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Height, Autoimmune Thyroid Disease, and Thyroid Cancer: A Mendelian Randomization Study.

Accepted version
Peer-reviewed

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Authors

Papadopoulou, Areti  ORCID logo  https://orcid.org/0000-0003-3158-7951
Burgess, Stephen 
Medici, Marco 

Abstract

Background: Increased height has been associated with increased risk of hypothyroidism or thyroid cancer in epidemiological studies. However, the potential causal association between height and hypothyroidism or thyroid cancer has not been thoroughly explored. Autoimmune thyroid disease (AITD) mainly presents as hypothyroidism, thus we aim to evaluate the causal relationship between height as exposure and its association with AITD or thyroid cancer. Methods: Mendelian randomization (MR) analyses were performed by using genetic instruments associated with height, which were selected from the largest genome-wide association meta-analysis for height in up to 5.4 million individuals. Summary-level data for AITD and thyroid cancer (including 30,234 and 3001 cases, respectively) were collected from the large number of available genome-wide association studies. Bidirectional MR was performed to test for reverse causal association between AITD and adult height. Results: MR analyses showed that increased genetically predicted height was associated with a 4% increased risk of AITD ([CI 1.02 to 1.07], p-value = 1.99E-03) per 1-standard deviation (SD) increase in genetically predicted height. The bidirectional MR did not show any causal association between AITD and adult height. Additionally, increased genetically predicted height was associated with 15% increased risk of thyroid cancer ([CI 1.07 to 1.23], p-value = 2.32E-04) per 1-SD increase in height. Sensitivity analysis confirmed the main results. Conclusions: This MR study showed that 1-SD increase in genetically predicted height was associated with increased risk of AITD and thyroid cancer. In contrast, there was no evidence of a causal association of genetically predicted AITD with height. These results could further aid in investigation of height-related pathways as a means of gaining new mechanistic insights into AITD and thyroid cancer.

Description

Keywords

Mendelian randomisation, autoimmune thyroid disease, height, thyroid cancer, Adult, Humans, Mendelian Randomization Analysis, Genome-Wide Association Study, Hashimoto Disease, Hypothyroidism, Thyroid Neoplasms, Polymorphism, Single Nucleotide

Journal Title

Thyroid

Conference Name

Journal ISSN

1050-7256
1557-9077

Volume Title

Publisher

Mary Ann Liebert Inc
Sponsorship
Wellcome Trust (225790/Z/22/Z)
Wellcome Trust (225790/Z/22/Z)
Medical Research Council (MC_UU_00002/7)
Wellcome Trust (100114/Z/12/Z)
Wellcome Trust (204623/Z/16/Z)