Novel associations for hypothyroidism include known autoimmune risk loci.

Hypothyroidism is the most common thyroid disorder, affecting about 5% of the general population. Here we present the current largest genome-wide association study of hypothyroidism, in 3,736 cases and 35,546 controls. Hypothyroidism was assessed via web-based questionnaires. We identify five genome...

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Autores principales:	Nicholas Eriksson, Joyce Y Tung, Amy K Kiefer, David A Hinds, Uta Francke, Joanna L Mountain, Chuong B Do
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4636ff4f8c3b48179250dec3b4c8bf15
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spelling	oai:doaj.org-article:4636ff4f8c3b48179250dec3b4c8bf152021-11-18T07:23:02ZNovel associations for hypothyroidism include known autoimmune risk loci.1932-620310.1371/journal.pone.0034442https://doaj.org/article/4636ff4f8c3b48179250dec3b4c8bf152012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22493691/?tool=EBIhttps://doaj.org/toc/1932-6203Hypothyroidism is the most common thyroid disorder, affecting about 5% of the general population. Here we present the current largest genome-wide association study of hypothyroidism, in 3,736 cases and 35,546 controls. Hypothyroidism was assessed via web-based questionnaires. We identify five genome-wide significant associations, three of which are well known to be involved in a large spectrum of autoimmune diseases: rs6679677 near PTPN22, rs3184504 in SH2B3, and rs2517532 in the HLA class I region (p-values 2.8·10(-13), 2.6·10(-12), and 1.3·10(-8), respectively). We also report associations with rs4915077 near VAV3 (p-value 7.5·10(-10)) and rs925489 near FOXE1 (p value 2.4·10(-19)). VAV3 is involved in immune function, and FOXE1 and PTPN22 have previously been associated with hypothyroidism. Although the HLA class I region and SH2B3 have previously been linked with a number of autoimmune diseases, this is the first report of their association with thyroid disease. The VAV3 association is also novel. We also show suggestive evidence of association for hypothyroidism with a SNP in the HLA class II region (independent of the other HLA association) as well as SNPs in CAPZB, PDE8B, and CTLA4. CAPZB and PDE8B have been linked to TSH levels and CTLA4 to a variety of autoimmune diseases. These results suggest heterogeneity in the genetic etiology of hypothyroidism, implicating genes involved in both autoimmune disorders and thyroid function. Using a genetic risk profile score based on the top association from each of the five genome-wide significant regions in our study, the relative risk between the highest and lowest deciles of genetic risk is 2.0.Nicholas ErikssonJoyce Y TungAmy K KieferDavid A HindsUta FranckeJoanna L MountainChuong B DoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34442 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicholas Eriksson Joyce Y Tung Amy K Kiefer David A Hinds Uta Francke Joanna L Mountain Chuong B Do Novel associations for hypothyroidism include known autoimmune risk loci.
description	Hypothyroidism is the most common thyroid disorder, affecting about 5% of the general population. Here we present the current largest genome-wide association study of hypothyroidism, in 3,736 cases and 35,546 controls. Hypothyroidism was assessed via web-based questionnaires. We identify five genome-wide significant associations, three of which are well known to be involved in a large spectrum of autoimmune diseases: rs6679677 near PTPN22, rs3184504 in SH2B3, and rs2517532 in the HLA class I region (p-values 2.8·10(-13), 2.6·10(-12), and 1.3·10(-8), respectively). We also report associations with rs4915077 near VAV3 (p-value 7.5·10(-10)) and rs925489 near FOXE1 (p value 2.4·10(-19)). VAV3 is involved in immune function, and FOXE1 and PTPN22 have previously been associated with hypothyroidism. Although the HLA class I region and SH2B3 have previously been linked with a number of autoimmune diseases, this is the first report of their association with thyroid disease. The VAV3 association is also novel. We also show suggestive evidence of association for hypothyroidism with a SNP in the HLA class II region (independent of the other HLA association) as well as SNPs in CAPZB, PDE8B, and CTLA4. CAPZB and PDE8B have been linked to TSH levels and CTLA4 to a variety of autoimmune diseases. These results suggest heterogeneity in the genetic etiology of hypothyroidism, implicating genes involved in both autoimmune disorders and thyroid function. Using a genetic risk profile score based on the top association from each of the five genome-wide significant regions in our study, the relative risk between the highest and lowest deciles of genetic risk is 2.0.
format	article
author	Nicholas Eriksson Joyce Y Tung Amy K Kiefer David A Hinds Uta Francke Joanna L Mountain Chuong B Do
author_facet	Nicholas Eriksson Joyce Y Tung Amy K Kiefer David A Hinds Uta Francke Joanna L Mountain Chuong B Do
author_sort	Nicholas Eriksson
title	Novel associations for hypothyroidism include known autoimmune risk loci.
title_short	Novel associations for hypothyroidism include known autoimmune risk loci.
title_full	Novel associations for hypothyroidism include known autoimmune risk loci.
title_fullStr	Novel associations for hypothyroidism include known autoimmune risk loci.
title_full_unstemmed	Novel associations for hypothyroidism include known autoimmune risk loci.
title_sort	novel associations for hypothyroidism include known autoimmune risk loci.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/4636ff4f8c3b48179250dec3b4c8bf15
work_keys_str_mv	AT nicholaseriksson novelassociationsforhypothyroidismincludeknownautoimmuneriskloci AT joyceytung novelassociationsforhypothyroidismincludeknownautoimmuneriskloci AT amykkiefer novelassociationsforhypothyroidismincludeknownautoimmuneriskloci AT davidahinds novelassociationsforhypothyroidismincludeknownautoimmuneriskloci AT utafrancke novelassociationsforhypothyroidismincludeknownautoimmuneriskloci AT joannalmountain novelassociationsforhypothyroidismincludeknownautoimmuneriskloci AT chuongbdo novelassociationsforhypothyroidismincludeknownautoimmuneriskloci
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Novel associations for hypothyroidism include known autoimmune risk loci.

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