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Thyroid Genetics and the Cardiovascular System

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Thyroid and Heart

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Abstract

Genetic factors are major determinants of thyroid function, and in the last two decades association studies have identified many genetic variants which are associated with thyroid-stimulating hormone (TSH) and thyroid hormone (TH) levels. In turn, thyroid function has been related to various cardiovascular diseases in observational studies. While both hypo- and hyperthyroidism have been associated with an increased risk of adverse cardiovascular outcomes, other studies showed that even minor variation in thyroid function within the normal range may affect the cardiovascular risk. In this chapter, we provide an overview of genetic factors involved in the regulation of thyroid function, and their relation with cardiovascular risk factors and outcomes. Moreover, we indicate how data from genetic association studies on thyroid function can be useful from a clinical perspective. Finally, we discuss current knowledge gaps and directions for future research.

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References

  1. Chaker L, et al. Subclinical hypothyroidism and the risk of stroke events and fatal stroke: an individual participant data analysis. J Clin Endocrinol Metab. 2015;100(6):2181–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Moon S, et al. Subclinical hypothyroidism and the risk of cardiovascular disease and all-cause mortality: a meta-analysis of prospective cohort studies. Thyroid. 2018;28(9):1101–10.

    Article  PubMed  Google Scholar 

  3. Dekkers OM, et al. Acute cardiovascular events and all-cause mortality in patients with hyperthyroidism: a population-based cohort study. Eur J Endocrinol. 2017;176(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  4. Collet TH, et al. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med. 2012;172(10):799–809.

    Article  CAS  PubMed  Google Scholar 

  5. Rodondi N, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010;304(12):1365–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bano A, et al. Thyroid function and the risk of atherosclerotic cardiovascular morbidity and mortality: the Rotterdam Study. Circ Res. 2017;121(12):1392–400.

    Article  CAS  PubMed  Google Scholar 

  7. Chaker L, et al. Thyroid function within the reference range and the risk of stroke: an individual participant data analysis. J Clin Endocrinol Metab. 2016;101(11):4270–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Andersen S, et al. Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab. 2002;87(3):1068–72.

    Article  CAS  PubMed  Google Scholar 

  9. Hansen PS, et al. Major genetic influence on the regulation of the pituitary-thyroid axis: a study of healthy Danish twins. J Clin Endocrinol Metab. 2004;89(3):1181–7.

    Article  CAS  PubMed  Google Scholar 

  10. Teumer A, et al. Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. Nat Commun. 2018;9(1):4455.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Medici M, et al. Genetic determination of the hypothalamic-pituitary-thyroid axis: where do we stand? Endocr Rev. 2015;36(2):214–44.

    Article  CAS  PubMed  Google Scholar 

  12. Effraimidis G, Wiersinga WM. Mechanisms in endocrinology: autoimmune thyroid disease: old and new players. Eur J Endocrinol. 2014;170(6):R241–52.

    Article  CAS  PubMed  Google Scholar 

  13. Ploski R, Szymanski K, Bednarczuk T. The genetic basis of Graves’ disease. Curr Genomics. 2011;12(8):542–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hansen PS, et al. The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population. Clin Endocrinol. 2007;66(6):827–32.

    Article  CAS  Google Scholar 

  15. Peeters RP, et al. Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects. J Clin Endocrinol Metab. 2003;88(6):2880–8.

    Article  CAS  PubMed  Google Scholar 

  16. van der Deure WM, et al. Effects of serum TSH and FT4 levels and the TSHR-Asp727Glu polymorphism on bone: the Rotterdam Study. Clin Endocrinol. 2008;68(2):175–81.

    Google Scholar 

  17. Gabriel EM, et al. Germline polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter. J Clin Endocrinol Metab. 1999;84(9):3328–35.

    CAS  PubMed  Google Scholar 

  18. Nogueira CR, et al. Thyrotropin receptor mutations in hyperfunctioning thyroid adenomas from Brazil. Thyroid. 1999;9(11):1063–8.

    Article  CAS  PubMed  Google Scholar 

  19. Sykiotis GP, et al. Functional significance of the thyrotropin receptor germline polymorphism D727E. Biochem Biophys Res Commun. 2003;301(4):1051–6.

    Article  CAS  PubMed  Google Scholar 

  20. Medici M, et al. A large-scale association analysis of 68 thyroid hormone pathway genes with serum TSH and FT4 levels. Eur J Endocrinol. 2011;164(5):781–8.

    Article  CAS  PubMed  Google Scholar 

  21. Lago-Leston R, et al. Prevalence and functional analysis of the S107P polymorphism (rs6647476) of the monocarboxylate transporter 8 (SLC16A2) gene in the male population of north-west Spain (Galicia). Clin Endocrinol. 2009;70(4):636–43.

    Article  CAS  Google Scholar 

  22. Roef GL, et al. Associations between single nucleotide polymorphisms in thyroid hormone transporter genes (MCT8, MCT10 and OATP1C1) and circulating thyroid hormones. Clin Chim Acta. 2013;425:227–32.

    Article  CAS  PubMed  Google Scholar 

  23. Ortiga-Carvalho TM, Sidhaye AR, Wondisford FE. Thyroid hormone receptors and resistance to thyroid hormone disorders. Nat Rev Endocrinol. 2014;10(10):582–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. van Gucht ALM, et al. Resistance to thyroid hormone due to heterozygous mutations in thyroid hormone receptor alpha. Curr Top Dev Biol. 2017;125:337–55.

    Article  PubMed  Google Scholar 

  25. Feng J, et al. Scanning of estrogen receptor alpha (ERalpha) and thyroid hormone receptor alpha (TRalpha) genes in patients with psychiatric diseases: four missense mutations identified in ERalpha gene. Am J Med Genet. 2001;105(4):369–74.

    Article  CAS  PubMed  Google Scholar 

  26. Sorensen HG, et al. Identification and consequences of polymorphisms in the thyroid hormone receptor alpha and beta genes. Thyroid. 2008;18(10):1087–94.

    Article  CAS  PubMed  Google Scholar 

  27. Arnaud-Lopez L, et al. Phosphodiesterase 8B gene variants are associated with serum TSH levels and thyroid function. Am J Hum Genet. 2008;82(6):1270–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gudmundsson J, et al. Discovery of common variants associated with low TSH levels and thyroid cancer risk. Nat Genet. 2012;44(3):319–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Porcu E, et al. A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function. PLoS Genet. 2013;9(2):e1003266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Panicker V, et al. A locus on chromosome 1p36 is associated with thyrotropin and thyroid function as identified by genome-wide association study. Am J Hum Genet. 2010;87(3):430–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rawal R, et al. Meta-analysis of two genome-wide association studies identifies four genetic loci associated with thyroid function. Hum Mol Genet. 2012;21(14):3275–82.

    Article  CAS  PubMed  Google Scholar 

  32. Malinowski JR, et al. Genetic variants associated with serum thyroid stimulating hormone (TSH) levels in European Americans and African Americans from the eMERGE network. PLoS One. 2014;9(12):e111301.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Nielsen TR, et al. A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents. PLoS One. 2017;12(3):e0174204.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Kwak SH, et al. A genome-wide association study on thyroid function and anti-thyroid peroxidase antibodies in Koreans. Hum Mol Genet. 2014;23(16):4433–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhan M, et al. Genome-wide association study identifies a novel susceptibility gene for serum TSH levels in Chinese populations. Hum Mol Genet. 2014;23(20):5505–17.

    Article  CAS  PubMed  Google Scholar 

  36. Lowe JK, et al. Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae. PLoS Genet. 2009;5(2):e1000365.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Peeters RP, et al. A polymorphism in type I deiodinase is associated with circulating free insulin-like growth factor I levels and body composition in humans. J Clin Endocrinol Metab. 2005;90(1):256–63.

    Article  CAS  PubMed  Google Scholar 

  38. de Jong FJ, et al. The association of polymorphisms in the type 1 and 2 deiodinase genes with circulating thyroid hormone parameters and atrophy of the medial temporal lobe. J Clin Endocrinol Metab. 2007;92(2):636–40.

    Article  PubMed  CAS  Google Scholar 

  39. Panicker V, et al. A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine. J Clin Endocrinol Metab. 2008;93(8):3075–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Philibert RA, et al. The relationship of deiodinase 1 genotype and thyroid function to lifetime history of major depression in three independent populations. Am J Med Genet B Neuropsychiatr Genet. 2011;156B(5):593–9.

    Article  PubMed  CAS  Google Scholar 

  41. Procopciuc LM, et al. The effect of the D1-C785T polymorphism in the type 1 iodothyronine deiodinase gene on the circulating thyroid hormone levels in Romanian women with preeclampsia. Association with the degree of severity and pregnancy outcome of preeclampsia. Gynecol Endocrinol. 2012;28(5):386–90.

    Article  CAS  PubMed  Google Scholar 

  42. Roef G, et al. Heredity and lifestyle in the determination of between-subject variation in thyroid hormone levels in euthyroid men. Eur J Endocrinol. 2013;169(6):835–44.

    Article  CAS  PubMed  Google Scholar 

  43. van der Deure WM, et al. The effect of genetic variation in the type 1 deiodinase gene on the interindividual variation in serum thyroid hormone levels: an investigation in healthy Danish twins. Clin Endocrinol. 2009;70(6):954–60.

    Article  CAS  Google Scholar 

  44. Peeters RP, et al. A new polymorphism in the type II deiodinase gene is associated with circulating thyroid hormone parameters. Am J Physiol Endocrinol Metab. 2005;289(1):E75–81.

    Article  CAS  PubMed  Google Scholar 

  45. Coppotelli G, et al. Functional characterization of the 258 A/G (D2-ORFa-Gly3Asp) human type-2 deiodinase polymorphism: a naturally occurring variant increases the enzymatic activity by removing a putative repressor site in the 5' UTR of the gene. Thyroid. 2006;16(7):625–32.

    Article  CAS  PubMed  Google Scholar 

  46. Pe’er I, et al. Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol. 2008;32(4):381–5.

    Article  PubMed  Google Scholar 

  47. Taylor PN, et al. Whole-genome sequence-based analysis of thyroid function. Nat Commun. 2015;6:5681.

    Article  CAS  PubMed  Google Scholar 

  48. Gudbjartsson DF, et al. Large-scale whole-genome sequencing of the Icelandic population. Nat Genet. 2015;47(5):435–44.

    Article  CAS  PubMed  Google Scholar 

  49. Cangul H, et al. A nonsense thyrotropin receptor gene mutation (R609X) is associated with congenital hypothyroidism and heart defects. J Pediatr Endocrinol Metab. 2014;27(11–12):1101–5.

    CAS  PubMed  Google Scholar 

  50. Marelli F, et al. In vivo functional consequences of human THRA variants expressed in the zebrafish. Thyroid. 2017;27(2):279–91.

    Article  CAS  PubMed  Google Scholar 

  51. Dentice M, et al. Missense mutation in the transcription factor NKX2-5: a novel molecular event in the pathogenesis of thyroid dysgenesis. J Clin Endocrinol Metab. 2006;91(4):1428–33.

    Article  CAS  PubMed  Google Scholar 

  52. Hermanns P, et al. Mutations in the NKX2.5 gene and the PAX8 promoter in a girl with thyroid dysgenesis. J Clin Endocrinol Metab. 2011;96(6):E977–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Narumi S, et al. Transcription factor mutations and congenital hypothyroidism: systematic genetic screening of a population-based cohort of Japanese patients. J Clin Endocrinol Metab. 2010;95(4):1981–5.

    Article  CAS  PubMed  Google Scholar 

  54. Passeri E, et al. Increased risk for non-autoimmune hypothyroidism in young patients with congenital heart defects. J Clin Endocrinol Metab. 2011;96(7):E1115–9.

    Article  CAS  PubMed  Google Scholar 

  55. Razvi S, et al. Thyroid hormones and cardiovascular function and diseases. J Am Coll Cardiol. 2018;71(16):1781–96.

    Article  CAS  PubMed  Google Scholar 

  56. Frost L, Vestergaard P, Mosekilde L. Hyperthyroidism and risk of atrial fibrillation or flutter: a population-based study. Arch Intern Med. 2004;164(15):1675–8.

    Article  PubMed  Google Scholar 

  57. Chaker L, et al. Normal thyroid function and the risk of atrial fibrillation: the Rotterdam Study. J Clin Endocrinol Metab. 2015;100(10):3718–24.

    Article  CAS  PubMed  Google Scholar 

  58. Baumgartner C, et al. Thyroid function within the normal range, subclinical hypothyroidism, and the risk of atrial fibrillation. Circulation. 2017;136(22):2100–16.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Hebrant A, et al. Genetic hyperthyroidism: hyperthyroidism due to activating TSHR mutations. Eur J Endocrinol. 2011;164(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  60. Singh BK, Yen PM. A clinician’s guide to understanding resistance to thyroid hormone due to receptor mutations in the TRalpha and TRbeta isoforms. Clin Diabetes Endocrinol. 2017;3:8.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Clarke SL, Assimes TL. Genome-wide association studies of coronary artery disease: recent progress and challenges ahead. Curr Atheroscler Rep. 2018;20(9):47.

    Article  PubMed  Google Scholar 

  62. Shu L, Blencowe M, Yang X. Translating GWAS findings to novel therapeutic targets for coronary artery disease. Front Cardiovasc Med. 2018;5:56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Jorde R, et al. The phosphodiesterase 8B gene rs4704397 is associated with thyroid function, risk of myocardial infarction, and body height: the Tromso study. Thyroid. 2014;24(2):215–22.

    Article  CAS  PubMed  Google Scholar 

  64. Medici M, Visser TJ, Peeters RP. Genetics of thyroid function. Best Pract Res Clin Endocrinol Metab. 2017;31(2):129–42.

    Article  CAS  PubMed  Google Scholar 

  65. Torpy JM, Burke AE, Glass RM. JAMA patient page. Coronary heart disease risk factors. JAMA. 2009;302(21):2388.

    Article  PubMed  Google Scholar 

  66. Ye Y, et al. Association between subclinical hypothyroidism and blood pressure—a meta-analysis of observational studies. Endocr Pract. 2014;20(2):150–8.

    Article  PubMed  Google Scholar 

  67. Prisant LM, Gujral JS, Mulloy AL. Hyperthyroidism: a secondary cause of isolated systolic hypertension. J Clin Hypertens (Greenwich). 2006;8(8):596–9.

    Article  Google Scholar 

  68. Asvold BO, et al. Association between blood pressure and serum thyroid-stimulating hormone concentration within the reference range: a population-based study. J Clin Endocrinol Metab. 2007;92(3):841–5.

    Article  PubMed  CAS  Google Scholar 

  69. Gumieniak O, et al. Ala92 type 2 deiodinase allele increases risk for the development of hypertension. Hypertension. 2007;49(3):461–6.

    Article  CAS  PubMed  Google Scholar 

  70. Maia AL, et al. Lack of association between the type 2 deiodinase A/G polymorphism and hypertensive traits: the Framingham Heart Study. Hypertension. 2008;51(4):e22–3.

    Article  CAS  PubMed  Google Scholar 

  71. Dora JM, et al. Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case-control study and meta-analysis. Eur J Endocrinol. 2010;163(3):427–34.

    Article  CAS  PubMed  Google Scholar 

  72. van der Deure WM, et al. Impact of thyroid function and polymorphisms in the type 2 deiodinase on blood pressure: the Rotterdam Study and the Rotterdam Scan Study. Clin Endocrinol. 2009;71(1):137–44.

    Article  CAS  Google Scholar 

  73. Goumidi L, et al. Association between a thyroid hormone receptor-alpha gene polymorphism and blood pressure but not with coronary heart disease risk. Am J Hypertens. 2011;24(9):1027–34.

    Article  CAS  PubMed  Google Scholar 

  74. Chaker L, et al. Thyroid function and risk of type 2 diabetes: a population-based prospective cohort study. BMC Med. 2016;14(1):150.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Peeters RP, et al. The Asp727Glu polymorphism in the TSH receptor is associated with insulin resistance in healthy elderly men. Clin Endocrinol. 2007;66(6):808–15.

    Article  CAS  Google Scholar 

  76. Mentuccia D, et al. Association between a novel variant of the human type 2 deiodinase gene Thr92Ala and insulin resistance: evidence of interaction with the Trp64Arg variant of the beta-3-adrenergic receptor. Diabetes. 2002;51(3):880–3.

    Article  CAS  PubMed  Google Scholar 

  77. Mentuccia D, et al. The Thr92Ala deiodinase type 2 (DIO2) variant is not associated with type 2 diabetes or indices of insulin resistance in the old order of Amish. Thyroid. 2005;15(11):1223–7.

    Article  PubMed  Google Scholar 

  78. Maia AL, et al. The type 2 deiodinase (DIO2) A/G polymorphism is not associated with glycemic traits: the Framingham Heart Study. Thyroid. 2007;17(3):199–202.

    Article  CAS  PubMed  Google Scholar 

  79. Grarup N, et al. Studies of the common DIO2 Thr92Ala polymorphism and metabolic phenotypes in 7342 Danish white subjects. J Clin Endocrinol Metab. 2007;92(1):363–6.

    Article  CAS  PubMed  Google Scholar 

  80. Senee V, et al. Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. Nat Genet. 2006;38(6):682–7.

    Article  CAS  PubMed  Google Scholar 

  81. Alexandrides T, Moses AC, Smith RJ. Developmental expression of receptors for insulin, insulin-like growth factor I (IGF-I), and IGF-II in rat skeletal muscle. Endocrinology. 1989;124(2):1064–76.

    Article  CAS  PubMed  Google Scholar 

  82. Feldt-Rasmussen U. Interactions between growth hormone and the thyroid gland -- with special reference to biochemical diagnosis. Curr Med Chem. 2007;14(26):2783–8.

    Article  CAS  PubMed  Google Scholar 

  83. Laron Z. Interactions between the thyroid hormones and the hormones of the growth hormone axis. Pediatr Endocrinol Rev. 2003;1(Suppl 2):244–9; discussion 250.

    PubMed  Google Scholar 

  84. Vincent AM, Feldman EL. Control of cell survival by IGF signaling pathways. Growth Hormon IGF Res. 2002;12(4):193–7.

    Article  CAS  Google Scholar 

  85. Grimes DA, Schulz KF. Bias and causal associations in observational research. Lancet. 2002;359(9302):248–52.

    Article  PubMed  Google Scholar 

  86. Zheng J, et al. Recent developments in Mendelian randomization studies. Curr Epidemiol Rep. 2017;4(4):330–45.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Burgess S, et al. Sensitivity analyses for robust causal inference from Mendelian randomization analyses with multiple genetic variants. Epidemiology. 2017;28(1):30–42.

    Article  PubMed  Google Scholar 

  88. Zhao JV, Schooling CM. Thyroid function and ischemic heart disease: a Mendelian randomization study. Sci Rep. 2017;7(1):8515.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Consortium CAD, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 2013;45(1):25–33.

    Article  CAS  Google Scholar 

  90. Wilson PW, et al. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97(18):1837–47.

    Article  CAS  PubMed  Google Scholar 

  91. Khera AV, et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018;50(9):1219–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Khera AV, et al. Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med. 2016;375(24):2349–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Knowles JW, Ashley EA. Cardiovascular disease: the rise of the genetic risk score. PLoS Med. 2018;15(3):e1002546.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Panicker V, et al. Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. J Clin Endocrinol Metab. 2009;94(5):1623–9.

    Article  CAS  PubMed  Google Scholar 

  95. Appelhof BC, et al. Polymorphisms in type 2 deiodinase are not associated with well-being, neurocognitive functioning, and preference for combined thyroxine/3,5,3′-triiodothyronine therapy. J Clin Endocrinol Metab. 2005;90(11):6296–9.

    Article  CAS  PubMed  Google Scholar 

  96. Medici M, et al. Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease. PLoS Genet. 2014;10(2):e1004123.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Schultheiss UT, et al. A genetic risk score for thyroid peroxidase antibodies associates with clinical thyroid disease in community-based populations. J Clin Endocrinol Metab. 2015;100(5):E799–807.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Chaker L, et al. Thyroid function characteristics and determinants: the Rotterdam Study. Thyroid. 2016;26(9):1195–204.

    Article  CAS  PubMed  Google Scholar 

  99. Canaris GJ, et al. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160(4):526–34.

    Article  CAS  PubMed  Google Scholar 

  100. Wiersinga WM, et al. 2012 ETA guidelines: the use of L-T4 + L-T3 in the treatment of hypothyroidism. Eur Thyroid J. 2012;1(2):55–71.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Manolio TA, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Aschard H, et al. Challenges and opportunities in genome-wide environmental interaction (GWEI) studies. Hum Genet. 2012;131(10):1591–613.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Ritchie MD, Van Steen K. The search for gene-gene interactions in genome-wide association studies: challenges in abundance of methods, practical considerations, and biological interpretation. Ann Transl Med. 2018;6(8):157.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Zuk O, et al. Searching for missing heritability: designing rare variant association studies. Proc Natl Acad Sci U S A. 2014;111(4):E455–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Parikh VN, Ashley EA. Next-generation sequencing in cardiovascular disease: present clinical applications and the horizon of precision medicine. Circulation. 2017;135(5):406–9.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Seidelmann SB, et al. Application of whole exome sequencing in the clinical diagnosis and management of inherited cardiovascular diseases in adults. Circ Cardiovasc Genet. 2017:10(1).

    Google Scholar 

  107. Khera AV, et al. Whole genome sequencing to characterize monogenic and polygenic contributions in patients hospitalized with early-onset myocardial infarction. Circulation. 2019;139:1593–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Trerotola M, et al. Epigenetic inheritance and the missing heritability. Hum Genomics. 2015;9:17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Fernandez-Sanles A, et al. Association between DNA methylation and coronary heart disease or other atherosclerotic events: a systematic review. Atherosclerosis. 2017;263:325–33.

    Article  CAS  PubMed  Google Scholar 

  110. Pietzner M, Kacprowski T, Friedrich N. Empowering thyroid hormone research in human subjects using OMICs technologies. J Endocrinol. 2018;238(1):R13–29.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

    Aleksander Kuś, Layal Chaker & Marco Medici

  2. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

    Aleksander Kuś, Layal Chaker & Marco Medici

  3. Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland

    Aleksander Kuś

  4. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

    Alexander Teumer

  5. DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany

    Alexander Teumer

  6. Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

    Marco Medici

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  1. Aleksander Kuś
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  2. Alexander Teumer
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  3. Layal Chaker
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  4. Marco Medici
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Correspondence to Marco Medici .

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Editors and Affiliations

  1. Institute of Clinical Physiology (IFC) National Research Council (CNR), Pisa, Italy

    Giorgio Iervasi

  2. Institute of Clinical Physiology (IFC) National Research Council (CNR), Pisa, Italy

    Alessandro Pingitore

  3. NYITCOM College of Osteopathic Medicine Biomedical Sciences Department, Old Westbury, NY, USA

    A.Martin Gerdes

  4. Institute of Clinical and Translational Medicine, Newcastle University/Queen Elizabeth Hospital, Newcastle upon Tyne, UK

    Salman Razvi

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Kuś, A., Teumer, A., Chaker, L., Medici, M. (2020). Thyroid Genetics and the Cardiovascular System. In: Iervasi, G., Pingitore, A., Gerdes, A., Razvi, S. (eds) Thyroid and Heart . Springer, Cham. https://doi.org/10.1007/978-3-030-36871-5_15

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