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

Areti Papadopoulou, Bjørn O Åsvold, Stephen Burgess, Aleksander Kuś, Marco Medici, Rosalie Sterenborg, Alexander Teumer, Panos Deloukas, Eirini Marouli

Journal: Thyroid : official journal of the American Thyroid Association 2023;33(12):1476-1482

PMID: 37772697

Free Full Text on PubMed Central View on PubMed

Plain Language Summary

Increased height, risk for thyroid cancer and poor thyroid function have been linked. However, causal relationships have not yet been determined. Autoimmune thyroid disease (AITD) is a disease where the body attacks its own thyroid gland resulting in impaired function. This Mendelian randomisation study aimed to use genetic studies to determine the association between AITD, thyroid cancer and height. The results showed that predicted height was associated with an increased risk of AITD and thyroid cancer but neither condition caused the other. It was concluded that increased height was associated with increased risk of AITD and thyroid cancer but were not because of each other. This study could be used by healthcare professionals to understand that height, AITD, and thyroid cancer may be linked but how is still unclear. This study could be used by healthcare professionals to understand that people with increased height may be at a higher risk for thyroid cancer and AITD.

Abstract

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. 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. MR analyses showed that increased genetically predicted height was associated with a 4% increased risk of AITD ([CI 1.02 to 1.07], -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], -value = 2.32E-04) per 1-SD increase in height. Sensitivity analysis confirmed the main results. 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.

Address: William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.; MRC Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom.; Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.; Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland.; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Internal Medicine, Academic Center for Thyroid Diseases, Rotterdam, The Netherlands.; Department of Internal Medicine, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.; Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.; William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.; Digital Environment Research Institute, Queen Mary University of London, London, United Kingdom.

DOI: 10.1089/thy.2023.0272