However, this would only lead to bias if the causal effects of higher fat mass increasing FT 3 levels are different in the children not studied in this study.
Although we cannot fully exclude this there was no substantial difference in our models after adjustment for relevant socioeconomic confounders. Furthermore, positive associations between adiposity and FT 3 were also observed when using different instrument combinations, suggesting that there is not a systematic and biasing effect of pleiotropy in this case. With regard to measurement of free thyroid hormones, biases have been reported 39 , whereas measured levels of free thyroid hormones in our study may not be entirely independent from thyroid-binding globulin levels, the striking difference observed in the associations between BMI allelic score and FT 3 and FT 4 makes a substantial impact from thyroid-binding globulin in our genetic analysis unlikely.
Previous analyses have also identified the association between thyroid hormone parameters and body composition was largely independent of thyroid-binding globulin Potentially, FT 3 levels may be reduced in children with recent illness before blood sampling, but this would have likely biased our genetic associations to the null. As well as providing insight into the regulation of FT 3 in children, our findings are potentially clinically relevant. Childhood obesity is common and rising 40 , and increased FT 3 levels arising from increasing fat mass may have long-term consequences, particularly at the population level as even modest variation in thyroid status within the population reference range has adverse phenotypic effects 3.
In conclusion, our analysis has indicated that BMI and adiposity causally increase FT 3 levels in children. More research is required to identify the causal mechanisms for this and the consequences of childhood obesity on this relationship. We thank all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. Oxford University Press is a department of the University of Oxford.
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Association of serum TSH with high body mass differs between smokers and never-smokers. Relations of thyroid function to body weight: cross-sectional and longitudinal observations in a community-based sample. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. TSH and free triiodothyronine concentrations are associated with weight loss in a lifestyle intervention and weight regain afterwards in obese children.
De Pergola. Free triiodothyronine and thyroid stimulating hormone are directly associated with waist circumference, independently of insulin resistance, metabolic parameters and blood pressure in overweight and obese women. Triiodothyronine and free thyroxine levels are differentially associated with metabolic profile and adiposity-related cardiovascular risk markers in euthyroid middle-aged subjects.
Thyroid hormone status within the physiological range affects bone mass and density in healthy men at the age of peak bone mass. Free thyroxine is an independent predictor of subcutaneous fat in euthyroid individuals. Body composition and metabolic parameters are associated with variation in thyroid hormone levels among euthyroid young men. Clustered environments and randomized genes: a fundamental distinction between conventional and genetic epidemiology. Association analyses of , individuals reveal 18 new loci associated with body mass index. Genome-wide association study of three-dimensional facial morphology identifies a variant in PAX3 associated with nasion position.
MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Fat mass exerts a greater effect on cortical bone mass in girls than boys. Predictive testing for complex diseases using multiple genes: fact or fiction? Materials provided by Garvan Institute of Medical Research.
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