Hwangbo Yul, Park Young Joo
Center for Thyroid Cancer, National Cancer Center, Goyang, Korea.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Endocrinol Metab (Seoul). 2018 Jun;33(2):175-184. doi: 10.3803/EnM.2018.33.2.175.
Thyroid diseases, including autoimmune thyroid diseases and thyroid cancer, are known to have high heritability. Family and twin studies have indicated that genetics plays a major role in the development of thyroid diseases. Thyroid function, represented by thyroid stimulating hormone (TSH) and free thyroxine (T4), is also known to be partly genetically determined. Before the era of genome-wide association studies (GWAS), the ability to identify genes responsible for susceptibility to thyroid disease was limited. Over the past decade, GWAS have been used to identify genes involved in many complex diseases, including various phenotypes of the thyroid gland. In GWAS of autoimmune thyroid diseases, many susceptibility loci associated with autoimmunity (human leukocyte antigen [HLA], protein tyrosine phosphatase, non-receptor type 22 [PTPN22], cytotoxic T-lymphocyte associated protein 4 [CTLA4], and interleukin 2 receptor subunit alpha [IL2RA]) or thyroid-specific genes (thyroid stimulating hormone receptor [TSHR] and forkhead box E1 [FOXE1]) have been identified. Regarding thyroid function, many susceptibility loci for levels of TSH and free T4 have been identified through genome-wide analyses. In GWAS of differentiated thyroid cancer, associations at FOXE1, MAP3K12 binding inhibitory protein 1 (MBIP)-NK2 homeobox 1 (NKX2-1), disrupted in renal carcinoma 3 (DIRC3), neuregulin 1 (NRG1), and pecanex-like 2 (PCNXL2) have been commonly identified in people of European and Korean ancestry, and many other susceptibility loci have been found in specific populations. Through GWAS of various thyroid-related phenotypes, many susceptibility loci have been found, providing insights into the pathogenesis of thyroid diseases and disease co-clustering within families and individuals.
甲状腺疾病，包括自身免疫性甲状腺疾病和甲状腺癌，具有较高的遗传度。家族研究和双生子研究表明，遗传学在甲状腺疾病的发生发展中起主要作用。甲状腺功能由促甲状腺激素（TSH）和游离甲状腺素（T4）表示，部分也由遗传决定。在全基因组关联研究（GWAS）时代之前，识别甲状腺疾病易感性相关基因的能力有限。在过去十年中，GWAS已被用于识别涉及许多复杂疾病的基因，包括甲状腺的各种表型。在自身免疫性甲状腺疾病的GWAS中，已鉴定出许多与自身免疫相关的易感位点（人类白细胞抗原[HLA]、蛋白酪氨酸磷酸酶非受体型22[PTPN22]、细胞毒性T淋巴细胞相关蛋白4[CTLA4]和白细胞介素2受体α亚基[IL2RA]）或甲状腺特异性基因（促甲状腺激素受体[TSHR]和叉头框E1[FOXE1]）。关于甲状腺功能，通过全基因组分析已鉴定出许多TSH和游离T4水平的易感位点。在分化型甲状腺癌的GWAS中，在欧洲和韩国血统人群中通常已鉴定出FOXE1、丝裂原活化蛋白激酶激酶12结合抑制蛋白1（MBIP）-NK2同源框1（NKX2-1）、肾癌缺失3（DIRC3）、神经调节蛋白1（NRG1）和类pecanex 2（PCNXL2）的关联，并且在特定人群中发现了许多其他易感位点。通过对各种甲状腺相关表型的GWAS，发现了许多易感位点，为甲状腺疾病的发病机制以及家庭和个体中的疾病共聚集提供了见解。
