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Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis

Authors
  • Brčić, L.1
  • Barić, A.2
  • Gračan, S.2
  • Brekalo, M.2
  • Kaličanin, D.1
  • Gunjača, I.1
  • Torlak Lovrić, V.2
  • Tokić, S.3
  • Radman, M.2
  • Škrabić, V.4
  • Miljković, A.5
  • Kolčić, I.5
  • Štefanić, M.6
  • Glavaš-Obrovac, L.3
  • Lessel, D.7
  • Polašek, O.5
  • Zemunik, T.1
  • Barbalić, M.1
  • Punda, A.2
  • Boraska Perica, V.1
  • 1 University of Split, Department of Medical Biology, School of Medicine, Šoltanska 2, Split, 21000, Croatia , Split (Croatia)
  • 2 University Hospital Split, Department of Nuclear Medicine, Split, Croatia , Split (Croatia)
  • 3 University of Osijek, Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, Osijek, Croatia , Osijek (Croatia)
  • 4 University Hospital Split, Department of Pediatrics, Split, Croatia , Split (Croatia)
  • 5 University of Split, Department of Public Health, School of Medicine, Split, Croatia , Split (Croatia)
  • 6 University of Osijek, Department of Nuclear Medicine and Oncology, Faculty of Medicine, Osijek, Croatia , Osijek (Croatia)
  • 7 University Medical Center Hamburg-Eppendorf, Institute of Human Genetics, Hamburg, Germany , Hamburg (Germany)
Type
Published Article
Journal
Journal of Endocrinological Investigation
Publisher
Springer-Verlag
Publication Date
Oct 03, 2018
Volume
42
Issue
5
Pages
567–576
Identifiers
DOI: 10.1007/s40618-018-0955-4
Source
Springer Nature
Keywords
License
Yellow

Abstract

PurposeHashimoto’s thyroiditis (HT) is the most common form of autoimmune thyroid diseases. Current knowledge of HT genetics is limited, and not a single genome-wide association study (GWAS) focusing exclusively on HT has been performed to date. In order to decipher genetic determinants of HT, we performed the first GWAS followed by replication in a total of 1443 individuals from Croatia.MethodsWe performed association analysis in a discovery cohort comprising 405 cases and 433 controls. We followed up 13 independent signals (P < 10−5) in 303 cases and 302 controls from two replication cohorts and then meta-analyzed results across discovery and replication datasets.ResultsWe identified three variants suggestively associated with HT: rs12944194 located 206 kb from SDK2 (P = 1.8 × 10−6), rs75201096 inside GNA14 (P = 2.41 × 10−5) and rs791903 inside IP6K3 (P = 3.16 × 10−5). Genetic risk score (GRS), calculated using risk alleles of these loci, accounted for 4.82% of the total HT variance, and individuals from the top GRS quartile had 2.76 times higher odds for HT than individuals from the lowest GRS quartile.ConclusionsAlthough discovered loci are implicated with susceptibility to HT for the first time, genomic regions harboring these loci exhibit good biological candidacy due to involvement in the regulation of the thyroid function and autoimmunity. Additionally, we observe genetic overlap between HT and several related traits, such as hypothyroidism, Graves’ disease and TPOAb. Our study adds a new knowledge of underlying HT genetics and sets a firm basis for further research.

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