Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis
| Autor: | Stana Tokić, V. Boraska Perica, M Radman, Ljubica Glavaš-Obrovac, Sanda Gračan, Dean Kaličanin, Ozren Polasek, Ana Barić, Ante Punda, V. Torlak Lovrić, Luka Brčić, Tatijana Zemunik, Ivana Gunjača, Marko Brekalo, Veselin Škrabić, Ivana Kolcic, D. Lessel, Mario Štefanić, Ana Miljković, Maja Barbalić |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Autoimmune thyroid disease Autoimmunity GWAS Genetics Hashimoto’s thyroiditis Hypothyroidism Adolescent Genotype Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Genome-wide association study Hashimoto Disease Disease Biology medicine.disease_cause Polymorphism Single Nucleotide Thyroiditis Young Adult 03 medical and health sciences 0302 clinical medicine Endocrinology medicine Humans Genetic Predisposition to Disease Aged Genetic association Aged 80 and over Thyroid Middle Aged Prognosis medicine.disease Phenotype medicine.anatomical_structure Quartile Case-Control Studies 030220 oncology & carcinogenesis Female Thyroid function Biomarkers Follow-Up Studies Genome-Wide Association Study |
| Zdroj: | Journal of Endocrinological Investigation. 42:567-576 |
| ISSN: | 1720-8386 |
| Popis: | PURPOSE: Hashimoto'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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: Although 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. |
| Databáze: | OpenAIRE |
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