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Paradoxical relationship between body mass index and thyroid hormone levels: a study using Mendelian randomization

Taylor, Peter ORCID:, Richmond, Rebecca, Davies, Neil, Sayers, Adrian, Stevenson, Kirsty, Woltersdorf, Wolfram, Taylor, Andrew, Groom, Alix, Northstone, Kate, Ring, Susan, Okosieme, Onyebuchi E., Rees, Dafydd Aled ORCID:, Nitsch, Dorothea, Williams, Graham R., Smith, George Davey, Gregory, John Welbourn ORCID:, Timpson, Nicholas J., Tobias, Jonathan H. and Dayan, Colin Mark ORCID: 2016. Paradoxical relationship between body mass index and thyroid hormone levels: a study using Mendelian randomization. Journal of Clinical Endocrinology & Metabolism 101 (2) , pp. 730-738. 10.1210/jc.2015-3505

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Context: Free T3 (FT3) has been positively associated with body mass index (BMI) in cross-sectional studies in healthy individuals. This is difficult to reconcile with clinical findings in pathological thyroid dysfunction. Objective: We aimed to investigate whether childhood adiposity influences FT3 levels. Design: Mendelian randomization using genetic variants robustly associated with BMI. Setting: Avon Longitudinal Study of Parents and Children, a population-based birth cohort. Participants: A total of 3014 children who had thyroid function measured at age 7, who also underwent dual x-ray absorptiometry scans at ages 9.9 and 15.5 years and have genetic data available. Main Outcome Measures: FT3. Results: Observationally at age 7 years, BMI was positively associated with FT3: β-standardized (β-[std]) = 0.12 (95% confidence interval [CI]: 0.08, 0.16), P = 4.02 × 10−10; whereas FT4 was negatively associated with BMI: β-(std) = −0.08 (95% CI: −0.12, −0.04), P = 3.00 × 10−5. These differences persisted after adjustment for age, sex, and early life environment. Genetic analysis indicated 1 allele change in BMI allelic score was associated with a 0.04 (95% CI: 0.03, 0.04) SD increase in BMI (P = 6.41 × 10−17). At age 7, a genetically determined increase in BMI of 1.89 kg/m2 was associated with a 0.22 pmol/L (95% CI: 0.07, 0.36) increase in FT3 (P = .004) but no substantial change in FT4 0.01 mmol/L, (95% CI: −0.37, 0.40), P = .96. Conclusion: Our analysis shows that children with a genetically higher BMI had higher FT3 but not FT4 levels, indicating that higher BMI/fat mass has a causal role in increasing FT3 levels. This may explain the paradoxical associations observed in observational analyses. Given rising childhood obesity levels, this relationship merits closer scrutiny

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Additional Information: First Published Online: November 23, 2015
Publisher: The Endocrine Society
ISSN: 0021-972X
Date of Acceptance: 18 November 2015
Last Modified: 15 May 2024 01:27

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