Paradoxical relationship between body mass index and thyroid hormone levels; a study using Mendelian Randomization.


Taylor, PN; Richmond, R; Davies, N; Sayers, A; Stevenson, K; Woltersdorf, W; Taylor, A; Groom, A; Northstone, K; Ring, S; Okosieme, O; Rees, A; Nitsch, D; Williams, GR; Smith, GD; Gregory, JW; Timpson, NJ; Tobias, JH; Dayan, CM; (2015) Paradoxical relationship between body mass index and thyroid hormone levels; a study using Mendelian Randomization. The Journal of clinical endocrinology and metabolism, 101 (2). pp. 730-8. ISSN 0021-972X DOI: https://doi.org/10.1210/jc.2015-3505

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Abstract

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.<br/> OBJECTIVE: We aimed to investigate whether childhood adiposity influences FT3 levels.<br/> DESIGN: Mendelian randomization using genetic variants robustly associated with BMI.<br/> SETTING: Avon Longitudinal Study of Parents and Children, a population-based birth cohort.<br/> 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.<br/> MAIN OUTCOME MEASURES: FT3.<br/> 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/m(2) 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.<br/> 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.<br/>

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Research Centre: EHR Research Group
Centre for Statistical Methodology
PubMed ID: 26595101
Web of Science ID: 378642700044
URI: http://researchonline.lshtm.ac.uk/id/eprint/2373872

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