Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis
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 p...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Brčić, L. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2018 |
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| Schlagwörter: |
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| Anmerkung: |
© Italian Society of Endocrinology (SIE) 2018 |
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| Übergeordnetes Werk: |
Enthalten in: Journal of endocrinological investigation - [S. l.] : Springer, 1978, 42(2018), 5 vom: 03. Okt., Seite 567-576 |
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| Übergeordnetes Werk: |
volume:42 ; year:2018 ; number:5 ; day:03 ; month:10 ; pages:567-576 |
| Links: |
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| DOI / URN: |
10.1007/s40618-018-0955-4 |
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| Katalog-ID: |
SPR036864757 |
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| 041 | |a eng | ||
| 100 | 1 | |a Brčić, L. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis |
| 264 | 1 | |c 2018 | |
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| 500 | |a © Italian Society of Endocrinology (SIE) 2018 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a Hashimoto’s thyroiditis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Autoimmunity |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Hypothyroidism |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a GWAS |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Genetics |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Autoimmune thyroid disease |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Barić, A. |4 aut | |
| 700 | 1 | |a Gračan, S. |4 aut | |
| 700 | 1 | |a Brekalo, M. |4 aut | |
| 700 | 1 | |a Kaličanin, D. |4 aut | |
| 700 | 1 | |a Gunjača, I. |4 aut | |
| 700 | 1 | |a Torlak Lovrić, V. |4 aut | |
| 700 | 1 | |a Tokić, S. |4 aut | |
| 700 | 1 | |a Radman, M. |4 aut | |
| 700 | 1 | |a Škrabić, V. |4 aut | |
| 700 | 1 | |a Miljković, A. |4 aut | |
| 700 | 1 | |a Kolčić, I. |4 aut | |
| 700 | 1 | |a Štefanić, M. |4 aut | |
| 700 | 1 | |a Glavaš-Obrovac, L. |4 aut | |
| 700 | 1 | |a Lessel, D. |4 aut | |
| 700 | 1 | |a Polašek, O. |4 aut | |
| 700 | 1 | |a Zemunik, T. |4 aut | |
| 700 | 1 | |a Barbalić, M. |4 aut | |
| 700 | 1 | |a Punda, A. |4 aut | |
| 700 | 1 | |a Boraska Perica, V. |4 aut | |
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10.1007/s40618-018-0955-4 doi (DE-627)SPR036864757 (SPR)s40618-018-0955-4-e DE-627 ger DE-627 rakwb eng Brčić, L. verfasserin aut Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Italian Society of Endocrinology (SIE) 2018 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. Hashimoto’s thyroiditis (dpeaa)DE-He213 Autoimmunity (dpeaa)DE-He213 Hypothyroidism (dpeaa)DE-He213 GWAS (dpeaa)DE-He213 Genetics (dpeaa)DE-He213 Autoimmune thyroid disease (dpeaa)DE-He213 Barić, A. aut Gračan, S. aut Brekalo, M. aut Kaličanin, D. aut Gunjača, I. aut Torlak Lovrić, V. aut Tokić, S. aut Radman, M. aut Škrabić, V. aut Miljković, A. aut Kolčić, I. aut Štefanić, M. aut Glavaš-Obrovac, L. aut Lessel, D. aut Polašek, O. aut Zemunik, T. aut Barbalić, M. aut Punda, A. aut Boraska Perica, V. aut Enthalten in Journal of endocrinological investigation [S. l.] : Springer, 1978 42(2018), 5 vom: 03. Okt., Seite 567-576 (DE-627)369556267 (DE-600)2119482-8 1720-8386 nnns volume:42 year:2018 number:5 day:03 month:10 pages:567-576 https://dx.doi.org/10.1007/s40618-018-0955-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 42 2018 5 03 10 567-576 |
| spelling |
10.1007/s40618-018-0955-4 doi (DE-627)SPR036864757 (SPR)s40618-018-0955-4-e DE-627 ger DE-627 rakwb eng Brčić, L. verfasserin aut Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Italian Society of Endocrinology (SIE) 2018 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. Hashimoto’s thyroiditis (dpeaa)DE-He213 Autoimmunity (dpeaa)DE-He213 Hypothyroidism (dpeaa)DE-He213 GWAS (dpeaa)DE-He213 Genetics (dpeaa)DE-He213 Autoimmune thyroid disease (dpeaa)DE-He213 Barić, A. aut Gračan, S. aut Brekalo, M. aut Kaličanin, D. aut Gunjača, I. aut Torlak Lovrić, V. aut Tokić, S. aut Radman, M. aut Škrabić, V. aut Miljković, A. aut Kolčić, I. aut Štefanić, M. aut Glavaš-Obrovac, L. aut Lessel, D. aut Polašek, O. aut Zemunik, T. aut Barbalić, M. aut Punda, A. aut Boraska Perica, V. aut Enthalten in Journal of endocrinological investigation [S. l.] : Springer, 1978 42(2018), 5 vom: 03. Okt., Seite 567-576 (DE-627)369556267 (DE-600)2119482-8 1720-8386 nnns volume:42 year:2018 number:5 day:03 month:10 pages:567-576 https://dx.doi.org/10.1007/s40618-018-0955-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 42 2018 5 03 10 567-576 |
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10.1007/s40618-018-0955-4 doi (DE-627)SPR036864757 (SPR)s40618-018-0955-4-e DE-627 ger DE-627 rakwb eng Brčić, L. verfasserin aut Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Italian Society of Endocrinology (SIE) 2018 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. Hashimoto’s thyroiditis (dpeaa)DE-He213 Autoimmunity (dpeaa)DE-He213 Hypothyroidism (dpeaa)DE-He213 GWAS (dpeaa)DE-He213 Genetics (dpeaa)DE-He213 Autoimmune thyroid disease (dpeaa)DE-He213 Barić, A. aut Gračan, S. aut Brekalo, M. aut Kaličanin, D. aut Gunjača, I. aut Torlak Lovrić, V. aut Tokić, S. aut Radman, M. aut Škrabić, V. aut Miljković, A. aut Kolčić, I. aut Štefanić, M. aut Glavaš-Obrovac, L. aut Lessel, D. aut Polašek, O. aut Zemunik, T. aut Barbalić, M. aut Punda, A. aut Boraska Perica, V. aut Enthalten in Journal of endocrinological investigation [S. l.] : Springer, 1978 42(2018), 5 vom: 03. Okt., Seite 567-576 (DE-627)369556267 (DE-600)2119482-8 1720-8386 nnns volume:42 year:2018 number:5 day:03 month:10 pages:567-576 https://dx.doi.org/10.1007/s40618-018-0955-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 42 2018 5 03 10 567-576 |
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10.1007/s40618-018-0955-4 doi (DE-627)SPR036864757 (SPR)s40618-018-0955-4-e DE-627 ger DE-627 rakwb eng Brčić, L. verfasserin aut Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Italian Society of Endocrinology (SIE) 2018 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. Hashimoto’s thyroiditis (dpeaa)DE-He213 Autoimmunity (dpeaa)DE-He213 Hypothyroidism (dpeaa)DE-He213 GWAS (dpeaa)DE-He213 Genetics (dpeaa)DE-He213 Autoimmune thyroid disease (dpeaa)DE-He213 Barić, A. aut Gračan, S. aut Brekalo, M. aut Kaličanin, D. aut Gunjača, I. aut Torlak Lovrić, V. aut Tokić, S. aut Radman, M. aut Škrabić, V. aut Miljković, A. aut Kolčić, I. aut Štefanić, M. aut Glavaš-Obrovac, L. aut Lessel, D. aut Polašek, O. aut Zemunik, T. aut Barbalić, M. aut Punda, A. aut Boraska Perica, V. aut Enthalten in Journal of endocrinological investigation [S. l.] : Springer, 1978 42(2018), 5 vom: 03. Okt., Seite 567-576 (DE-627)369556267 (DE-600)2119482-8 1720-8386 nnns volume:42 year:2018 number:5 day:03 month:10 pages:567-576 https://dx.doi.org/10.1007/s40618-018-0955-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 42 2018 5 03 10 567-576 |
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10.1007/s40618-018-0955-4 doi (DE-627)SPR036864757 (SPR)s40618-018-0955-4-e DE-627 ger DE-627 rakwb eng Brčić, L. verfasserin aut Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Italian Society of Endocrinology (SIE) 2018 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. Hashimoto’s thyroiditis (dpeaa)DE-He213 Autoimmunity (dpeaa)DE-He213 Hypothyroidism (dpeaa)DE-He213 GWAS (dpeaa)DE-He213 Genetics (dpeaa)DE-He213 Autoimmune thyroid disease (dpeaa)DE-He213 Barić, A. aut Gračan, S. aut Brekalo, M. aut Kaličanin, D. aut Gunjača, I. aut Torlak Lovrić, V. aut Tokić, S. aut Radman, M. aut Škrabić, V. aut Miljković, A. aut Kolčić, I. aut Štefanić, M. aut Glavaš-Obrovac, L. aut Lessel, D. aut Polašek, O. aut Zemunik, T. aut Barbalić, M. aut Punda, A. aut Boraska Perica, V. aut Enthalten in Journal of endocrinological investigation [S. l.] : Springer, 1978 42(2018), 5 vom: 03. Okt., Seite 567-576 (DE-627)369556267 (DE-600)2119482-8 1720-8386 nnns volume:42 year:2018 number:5 day:03 month:10 pages:567-576 https://dx.doi.org/10.1007/s40618-018-0955-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 42 2018 5 03 10 567-576 |
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Enthalten in Journal of endocrinological investigation 42(2018), 5 vom: 03. Okt., Seite 567-576 volume:42 year:2018 number:5 day:03 month:10 pages:567-576 |
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Brčić, L. @@aut@@ Barić, A. @@aut@@ Gračan, S. @@aut@@ Brekalo, M. @@aut@@ Kaličanin, D. @@aut@@ Gunjača, I. @@aut@@ Torlak Lovrić, V. @@aut@@ Tokić, S. @@aut@@ Radman, M. @@aut@@ Škrabić, V. @@aut@@ Miljković, A. @@aut@@ Kolčić, I. @@aut@@ Štefanić, M. @@aut@@ Glavaš-Obrovac, L. @@aut@@ Lessel, D. @@aut@@ Polašek, O. @@aut@@ Zemunik, T. @@aut@@ Barbalić, M. @@aut@@ Punda, A. @@aut@@ Boraska Perica, V. @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR036864757</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519225730.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2018 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s40618-018-0955-4</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR036864757</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s40618-018-0955-4-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Brčić, L.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© Italian Society of Endocrinology (SIE) 2018</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">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. 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Brčić, L. |
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Brčić, L. misc Hashimoto’s thyroiditis misc Autoimmunity misc Hypothyroidism misc GWAS misc Genetics misc Autoimmune thyroid disease Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis |
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Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis Hashimoto’s thyroiditis (dpeaa)DE-He213 Autoimmunity (dpeaa)DE-He213 Hypothyroidism (dpeaa)DE-He213 GWAS (dpeaa)DE-He213 Genetics (dpeaa)DE-He213 Autoimmune thyroid disease (dpeaa)DE-He213 |
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Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis |
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Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis |
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Brčić, L. |
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Journal of endocrinological investigation |
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Brčić, L. Barić, A. Gračan, S. Brekalo, M. Kaličanin, D. Gunjača, I. Torlak Lovrić, V. Tokić, S. Radman, M. Škrabić, V. Miljković, A. Kolčić, I. Štefanić, M. Glavaš-Obrovac, L. Lessel, D. Polašek, O. Zemunik, T. Barbalić, M. Punda, A. Boraska Perica, V. |
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Elektronische Aufsätze |
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Brčić, L. |
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10.1007/s40618-018-0955-4 |
| title_sort |
genome-wide association analysis suggests novel loci for hashimoto’s thyroiditis |
| title_auth |
Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis |
| abstract |
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. © Italian Society of Endocrinology (SIE) 2018 |
| abstractGer |
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. © Italian Society of Endocrinology (SIE) 2018 |
| abstract_unstemmed |
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. © Italian Society of Endocrinology (SIE) 2018 |
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Genome-wide association analysis suggests novel loci for Hashimoto’s thyroiditis |
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https://dx.doi.org/10.1007/s40618-018-0955-4 |
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Barić, A. Gračan, S. Brekalo, M. Kaličanin, D. Gunjača, I. Torlak Lovrić, V. Tokić, S. Radman, M. Škrabić, V. Miljković, A. Kolčić, I. Štefanić, M. Glavaš-Obrovac, L. Lessel, D. Polašek, O. Zemunik, T. Barbalić, M. Punda, A. Boraska Perica, V. |
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Barić, A. Gračan, S. Brekalo, M. Kaličanin, D. Gunjača, I. Torlak Lovrić, V. Tokić, S. Radman, M. Škrabić, V. Miljković, A. Kolčić, I. Štefanić, M. Glavaš-Obrovac, L. Lessel, D. Polašek, O. Zemunik, T. Barbalić, M. Punda, A. Boraska Perica, V. |
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| score |
7.39818 |