You are here
Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease.
Tuesday,2014-04-01 12:57 America/Los_Angeles — poolea2
| Title | Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Medici, M, Porcu, E, Pistis, G, Teumer, A, Brown, SJ, Jensen, RA, Rawal, R, Roef, GL, Plantinga, TS, Vermeulen, SH, Lahti, J, Simmonds, MJ, Husemoen, LLotte N, Freathy, RM, Shields, BM, Pietzner, D, Nagy, R, Broer, L, Chaker, L, Korevaar, TIM, Plia, MGrazia, Sala, C, Völker, U, J Richards, B, Sweep, FC, Gieger, C, Corre, T, Kajantie, E, Thuesen, B, Taes, YE, W Visser, E, Hattersley, AT, Kratzsch, J, Hamilton, A, Li, W, Homuth, G, Lobina, M, Mariotti, S, Soranzo, N, Cocca, M, Nauck, M, Spielhagen, C, Ross, A, Arnold, A, van de Bunt, M, Liyanarachchi, S, Heier, M, Grabe, HJörgen, Masciullo, C, Galesloot, TE, Lim, EM, Reischl, E, Leedman, PJ, Lai, S, Delitala, A, Bremner, AP, Philips, DIW, Beilby, JP, Mulas, A, Vocale, M, Abecasis, G, Forsen, T, James, A, Widen, E, Hui, J, Prokisch, H, Rietzschel, EE, Palotie, A, Feddema, P, Fletcher, SJ, Schramm, K, Rotter, JI, Kluttig, A, Radke, D, Traglia, M, Surdulescu, GL, He, H, Franklyn, JA, Tiller, D, Vaidya, B, De Meyer, T, Jørgensen, T, Eriksson, JG, O'Leary, PC, Wichmann, E, Hermus, AR, Psaty, BM, Ittermann, T, Hofman, A, Bosi, E, Schlessinger, D, Wallaschofski, H, Pirastu, N, Aulchenko, YS, de la Chapelle, A, Netea-Maier, RT, Gough, SCL, Schwabedissen, HMeyer Zu, Frayling, TM, Kaufman, J-M, Linneberg, A, Räikkönen, K, Smit, JWA, Kiemeney, LA, Rivadeneira, F, Uitterlinden, AG, Walsh, JP, Meisinger, C, Heijer, Mden, Visser, TJ, Spector, TD, Wilson, SG, Völzke, H, Cappola, A, Toniolo, D, Sanna, S, Naitza, S, Peeters, RP |
| Journal | PLoS Genet |
| Volume | 10 |
| Issue | 2 |
| Pagination | e1004123 |
| Date Published | 2014 Feb |
| ISSN | 1553-7404 |
| Keywords | Autoantibodies, Genetic Loci, Genome-Wide Association Study, Graves Disease, Hashimoto Disease, Humans, Iodide Peroxidase, Risk Factors, Thyroiditis, Autoimmune, Thyrotropin |
| Abstract | <p>Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10(-8)) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68-2.81, P = 8.1×10(-8)), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26-1.82, P = 2.9×10(-6)), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66-0.89, P = 6.5×10(-4)). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22-1.54, P = 1.2×10(-7) and OR: 1.25, 95% CI 1.12-1.39, P = 6.2×10(-5)). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18-2.10, P = 1.9×10(-3)). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which TPOAb-positives are particularly at risk of developing clinical thyroid dysfunction. </p> |
| DOI | 10.1371/journal.pgen.1004123 |
| Alternate Journal | PLoS Genet. |
| PubMed ID | 24586183 |
| PubMed Central ID | PMC3937134 |
| Grant List | UL1RR033176 / RR / NCRR NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States HL105756 / HL / NHLBI NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States WT089062 / / Wellcome Trust / United Kingdom P30 DK063491 / DK / NIDDK NIH HHS / United States P30 CA16058 / CA / NCI NIH HHS / United States P30 CA016058 / CA / NCI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States HL080295 / HL / NHLBI NIH HHS / United States P01 CA124570 / CA / NCI NIH HHS / United States AG023629 / AG / NIA NIH HHS / United States 085541/Z/08/Z / / Wellcome Trust / United Kingdom |