Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    Identification of novel genetic loci associated with thyroid peroxidase antibodies and clinical thyroid disease

    Access Status
    Open access via publisher
    Authors
    O'Leary, Peter
    Date
    2014
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Medici, M. and Porcu, E. and Pistis, G. and Teumer, A. and Brown, S. and Jensen, R. and Rawal, R. et al. 2014. Identification of novel genetic loci associated with thyroid peroxidase antibodies and clinical thyroid disease. PLos Genetics. 10 (2): Article ID e1004123.
    Source Title
    PLos Genetics
    DOI
    10.1371/journal.pgen.1004123
    ISSN
    1553-7390
    URI
    http://hdl.handle.net/20.500.11937/28641
    Collection
    • Curtin Research Publications
    Abstract

    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.

    Related items

    Showing items related by title, author, creator and subject.

    • Subclinical thyroid dysfunction and circulating thyroid hormones are not associated with bone turnover markers or incident hip fracture in older men
      Siru, R.; Alfonso, Helman; Chubb, S.; Golledge, J.; Flicker, L.; Yeap, B. (2018)
      © 2018 John Wiley & Sons Ltd Objective: Overt thyroid dysfunction is a risk factor for osteoporosis and fractures. Subclinical hyperthyroidism has also been associated with fracture. It remains unclear whether variation ...
    • Higher free thyroxine levels are associated with all-cause mortality in euthyroid older men: The Health in Men Study
      Yeap, B.; Alfonso, Helman; Hankey, G.; Flicker, L.; Golledge, J.; Norman, P.; Chubb, S. (2013)
      Objective: Thyroid dysfunction predicts poorer health outcomes, but the relationship between thyroid hormone levels within the reference range and mortality in older adults remains unclear. In this study, we examined the ...
    • Higher free thyroxine levels predict increased incidence of dementia in older men: The health in men study
      Yeap, B.; Alfonso, Helman; Chubb, S.; Puri, G.; Hankey, G.; Flicker, L.; Almeida, O. (2012)
      Context: Both hypothyroidism and subclinical hyperthyroidism hinder cognitive function. Objective: We aimed to determine whether more subtle alterations of thyroid hormone levels predict increased incidence of dementia ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.