Table 2. Susceptibility Loci for Levels of Thyroid Stimulating Hormone or Free Thyroxine Detected by Genome-Wide Association Studies.
| Phenotypes | Locus | Gene | Protein function | Population | Reference |
|---|---|---|---|---|---|
| TSH | 5q13.3 | PDE8B | Role in hydrolysis of the second messenger cAMP | European, USA, Germany, UK | [38,40,48,49] |
| 6q27 | PDE10A | Role in regulation of the intracellular concentration of cyclic nucleotides | European, UK | [38,40] | |
| 1p36.13 | CAPZB | Regulating actin filament dynamics | European, Chinese Han, Germany, UK | [38,39,40,49] | |
| 16q23.2 | MAF | Role in increased T-cell susceptibility to apoptosis | European, UK, Germany | [38,40,49] | |
| 6p21.1 | VEGFA | Proliferation and migration of vascular endothelial cells | European, UK | [38,40] | |
| 4q31.23 | NR3C2 | Role in aldosterone actions | European, Germany, UK | [38,40,49] | |
| 2q35 | IGFBP5 | Encoding insulin like growth factor binding protein 5 | European | [38] | |
| 17q24.3 | SOX9 | Role in chondrocyte differentiation | European | [38] | |
| 1p31.3 | NFIA | Encoding nuclear factor IA | European | [38] | |
| 15q21.2 | FGF7 | Mitogenic and cell survival activities | European | [38] | |
| 11p11.2 | PRDM11 | Role in transcription regulation | European | [38] | |
| 15q26.1 | MIR1179 | MicroRNA 1179 | European | [38] | |
| 19p13.2 | INSR | Encoding insulin receptor | European | [38] | |
| 9q34.2 | ABO | Determination of ABO blood group | European, UK | [38,40] | |
| 14q32.12 | ITPK1 | Regulation of the synthesis of inositol tetraphosphate | European | [38] | |
| 8p12 | NRG1 | Role in the growth and development of multiple organ systems | European | [38] | |
| 14q13.3 | MBIP-NKX2-1 | Encoding TTF-1, binding to TG promoter | European, UK | [38,40] | |
| 6q24.3 | SASH1 | Role in the TLR4 signaling pathway | European | [38] | |
| 9p24.2 | GLIS3 | Role in transcription in thyroid gland | European | [38] | |
| 8q12.1 | XKR4 | Role in apoptosis | Chinese Han | [39] | |
| 9q22.33 | FOXE1 | Encoding TTF-2, role in thyroid morphogenesis | Chinese Han, USA, UK | [39,40,48] | |
| 2q35 | IGFBP2 | Encoding insulin like growth factor binding protein 2 | UK | [40] | |
| 3p25.2 | SYN2 | Binding to small synaptic vesicles | UK | [40] | |
| Free T4 | 1p32.3 | DIO1 | Encoding iodothyronine deiodinase 1 | European, UK | [38,40] |
| 9q34.3 | LHX3 | Role in pituitary development | European, UK | [38,40] | |
| 9q22.33 | FOXE1 | Encoding TTF-2, role in thyroid morphogenesis | European | [38] | |
| 4q33 | AADAT | Role in L-lysine catabolism | European, UK | [38,40] | |
| 16q12.2 | LPCAT2-CAPNS2 | Role in membrane biogenesis | European | [38] | |
| 18q22.3 | NETO1-FBXO15 | Role in spatial learning and memory in the hippocampus | European | [38] | |
| 18q12.1 | B4GALT6 | Role in biosynthesis of glycosphingolipids | UK | [40] |
TSH, thyroid stimulating hormone; PDE8B, phosphodiesterase 8B; cAMP, cyclic adenosine monophosphate; PDE10A, phosphodiesterase 10A; CAPZB, capping actin protein of muscle Z-line subunit beta; VEGFA, vascular endothelial growth factor A; NR3C2, nuclear receptor subfamily 3 group C member 2; IGFBP5, insulin like growth factor binding protein 5; SOX9, SRY-box 9; NFIA, nuclear factor I A; FGF7, fibroblast growth factor 7; PRDM11, PR/SET domain 11; MIR1179, microRNA 1179; INSR, insulin receptor; ITPK1, inositol-tetrakisphosphate 1-kinase; NRG1, neuregulin 1; MBIP, MAP3K12 binding inhibitory protein 1; NKX2-1, NK2 homeobox 1; TTF, thyroid transcription factor; TG, thyroglobulin; SASH1, SAM and SH3 domain containing 1; TLR4, Toll-like receptor 4; GLIS3, GLIS family zinc finger 3; XKR4, XK related 4; FOXE1, forkhead box E1; IGFBP2, insulin like growth factor binding protein 2; SYN2, synapsin II; T4, thyroxine; DIO1, iodothyronine deiodinase 1; LHX3, LIM homeobox 3; AADAT, aminoadipate aminotransferase; LPCAT2, lysophosphatidylcholine acyltransferase 2; CAPNS2, calpain small subunit 2; NETO1, neuropilin and tolloid like 1; FBXO15, F-box protein 15; B4GALT6, beta-1,4-galactosyltransferase 6.