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Department of Genetics (P.B.S., P.W.Z., L.M.H., A.G.C., M.C.M., H.H.G., J.B.), Southwest Foundation for Biomedical Research, San Antonio, Texas 78245; Department of Human Genetics (G.P., C.M.K., D.F., M.M.B.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261; and Division of Pediatric Endocrinology (D.F., T.P.F.), Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213
Address all correspondence and requests for reprints to: Paul B. Samollow, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, Texas 78245-0549. E-mail: pbs{at}darwin.sfbr.org.
Thyroid hormones play major roles in the regulation of a wide range of metabolic and physiologic processes, but the genes and environmental factors that affect normal, quantitative variation in thyroid hormone concentrations are largely unknown. Using quantitative genetic methods, we evaluated the effects of genes and environmental factors on thyroid hormone variation in 586 women and 425 men from 27 randomly ascertained Mexican-American families from the San Antonio Family Heart Study. Data were available on free and total T4, free and total T3, TSH, thyroglobulin, and T4-binding globulin, as well as on covariates, including sex, age, weight, lifestyle habits, physical activity, and others. These covariates accounted for 2–18% of total phenotypic variation, whereas genes accounted for 26–64% of the variation. Overall, free T3 had the highest heritability, which is noteworthy because it is the most biologically active thyroid hormone and accounts for the vast majority of metabolic and physiologic effects of thyroid hormones. Our results indicate that genes account for a substantial portion of variation in human thyroid hormone levels, and suggest that further studies to identify the genes involved in this variation could reveal important insights into the processes that govern thyroid-mediated metabolism.
This work was supported by Research Grants RO1-DK57003 (to P.B.S.) and PO1-HL45522 awarded by the National Institutes of Health.
Abbreviations: CV, Coefficient(s) of variation; FT3, free T3; FT4, free T4; h2, heritability; NHANES, National Health and Nutrition Examination Survey; SAFHS, San Antonio Family Heart Study; SNP, single-nucleotide polymorphism; TBG, T4-binding globulin; TG, thyroglobulin; TGAb, antibodies against TG; TT3, total T3; TT4, total T4.
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