How much of the predisposition to Hashimoto's thyroiditis can be explained based on previously reported associations?

2018
journal article
article
18
cris.lastimport.wos2024-04-10T01:14:44Z
dc.abstract.enPurpose Our insight in the genetics of Hashimoto’s thyroiditis (HT) has become clearer through information provided by genome-wide association studies and candidate gene studies, but remains still not fully understood. Our aim was to assess how many different genetic risk variants contribute to the development of HT. Methods 147 HT cases (10.2% men) and 147 controls (13.6% men) were qualified for the analysis. Intrinsic and environmental factors were controlled for. Polymorphisms (SNP) were chosen based on the literature and included markers of the genes PTPN22, CTLA4, TG, TPO among others, and of genomic regions pointed by GWAS studies. SNP were typed on a microarray. Variants in the HLA-DRB1 gene were identified by Sanger sequencing. Results Multivariate predisposition to HT was modeled. Based on the investigated group, a model of seven variables was obtained. The variability explained by this model was assessed at only 5.4821% (p = 2 × 10-6), which indicates that many dozens of factors are required simultaneously to explain HT predisposition. Conclusions We analyzed genetic regions commonly and most significantly associated with autoimmune thyroid disorders in the literature, on a carefully selected cohort. Our results indicated a lack of possibility to predict the risk of HT development, even with a multivariate model. We therefore conclude that strong associations of single genetic regions with HT should be interpreted with great caution. We believe that a change in the attitude towards genetic association analyses of HT predisposition is necessary. Studies including multiple factors simultaneously are needed to unravel the intricacies of genetic associations with HT.pl
dc.affiliationWydział Lekarski : Klinika Endokrynologiipl
dc.affiliationWydział Lekarski : Ośrodek Genomiki Medycznej - OMICRONpl
dc.affiliationWydział Lekarski : Klinika Chorób Metabolicznychpl
dc.cm.date2020-01-07
dc.cm.id89851
dc.contributor.authorJabrocka-Hybel, Agata - 161547 pl
dc.contributor.authorSkalniak, Anna - 157273 pl
dc.contributor.authorPiątkowski, J.pl
dc.contributor.authorTurek-Jabrocka, Renata - 243250 pl
dc.contributor.authorVyhouskaya, Palinapl
dc.contributor.authorLudwig-Słomczyńska, Agnieszka - 212695 pl
dc.contributor.authorMachlowska, Julita - 139695 pl
dc.contributor.authorKapusta, Przemysław - 214546 pl
dc.contributor.authorMałecki, Maciej - 130840 pl
dc.contributor.authorPach, Dorota - 133063 pl
dc.contributor.authorTrofimiuk-Müldner, Małgorzata - 133685 pl
dc.contributor.authorLiziz-Kolus, K.pl
dc.contributor.authorHubalewska-Dydejczyk, Alicja - 129732 pl
dc.date.accessioned2020-01-17T09:59:58Z
dc.date.available2020-01-17T09:59:58Z
dc.date.issued2018pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.number12pl
dc.description.physical1409-1416pl
dc.description.points15pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume41pl
dc.identifier.doi10.1007/s40618-018-0910-4pl
dc.identifier.eissn1720-8386
dc.identifier.issn0391-4097pl
dc.identifier.projectROD UJ / OPpl
dc.identifier.urihttps://ruj.uj.edu.pl/xmlui/handle/item/143541
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa*
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl*
dc.share.typeinne
dc.subject.enHashimoto thyroiditispl
dc.subject.engeneticspl
dc.subject.enautoimmunepl
dc.subject.enpolymorphismpl
dc.subject.enHLApl
dc.subtypeArticlepl
dc.titleHow much of the predisposition to Hashimoto's thyroiditis can be explained based on previously reported associations?pl
dc.title.journalJournal of Endocrinological Investigationpl
dc.typeJournalArticlepl
dspace.entity.typePublication
cris.lastimport.wos
2024-04-10T01:14:44Z
dc.abstract.enpl
Purpose Our insight in the genetics of Hashimoto’s thyroiditis (HT) has become clearer through information provided by genome-wide association studies and candidate gene studies, but remains still not fully understood. Our aim was to assess how many different genetic risk variants contribute to the development of HT. Methods 147 HT cases (10.2% men) and 147 controls (13.6% men) were qualified for the analysis. Intrinsic and environmental factors were controlled for. Polymorphisms (SNP) were chosen based on the literature and included markers of the genes PTPN22, CTLA4, TG, TPO among others, and of genomic regions pointed by GWAS studies. SNP were typed on a microarray. Variants in the HLA-DRB1 gene were identified by Sanger sequencing. Results Multivariate predisposition to HT was modeled. Based on the investigated group, a model of seven variables was obtained. The variability explained by this model was assessed at only 5.4821% (p = 2 × 10-6), which indicates that many dozens of factors are required simultaneously to explain HT predisposition. Conclusions We analyzed genetic regions commonly and most significantly associated with autoimmune thyroid disorders in the literature, on a carefully selected cohort. Our results indicated a lack of possibility to predict the risk of HT development, even with a multivariate model. We therefore conclude that strong associations of single genetic regions with HT should be interpreted with great caution. We believe that a change in the attitude towards genetic association analyses of HT predisposition is necessary. Studies including multiple factors simultaneously are needed to unravel the intricacies of genetic associations with HT.
dc.affiliationpl
Wydział Lekarski : Klinika Endokrynologii
dc.affiliationpl
Wydział Lekarski : Ośrodek Genomiki Medycznej - OMICRON
dc.affiliationpl
Wydział Lekarski : Klinika Chorób Metabolicznych
dc.cm.date
2020-01-07
dc.cm.id
89851
dc.contributor.authorpl
Jabrocka-Hybel, Agata - 161547
dc.contributor.authorpl
Skalniak, Anna - 157273
dc.contributor.authorpl
Piątkowski, J.
dc.contributor.authorpl
Turek-Jabrocka, Renata - 243250
dc.contributor.authorpl
Vyhouskaya, Palina
dc.contributor.authorpl
Ludwig-Słomczyńska, Agnieszka - 212695
dc.contributor.authorpl
Machlowska, Julita - 139695
dc.contributor.authorpl
Kapusta, Przemysław - 214546
dc.contributor.authorpl
Małecki, Maciej - 130840
dc.contributor.authorpl
Pach, Dorota - 133063
dc.contributor.authorpl
Trofimiuk-Müldner, Małgorzata - 133685
dc.contributor.authorpl
Liziz-Kolus, K.
dc.contributor.authorpl
Hubalewska-Dydejczyk, Alicja - 129732
dc.date.accessioned
2020-01-17T09:59:58Z
dc.date.available
2020-01-17T09:59:58Z
dc.date.issuedpl
2018
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.numberpl
12
dc.description.physicalpl
1409-1416
dc.description.pointspl
15
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
41
dc.identifier.doipl
10.1007/s40618-018-0910-4
dc.identifier.eissn
1720-8386
dc.identifier.issnpl
0391-4097
dc.identifier.projectpl
ROD UJ / OP
dc.identifier.uri
https://ruj.uj.edu.pl/xmlui/handle/item/143541
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights*
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri*
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
inne
dc.subject.enpl
Hashimoto thyroiditis
dc.subject.enpl
genetics
dc.subject.enpl
autoimmune
dc.subject.enpl
polymorphism
dc.subject.enpl
HLA
dc.subtypepl
Article
dc.titlepl
How much of the predisposition to Hashimoto's thyroiditis can be explained based on previously reported associations?
dc.title.journalpl
Journal of Endocrinological Investigation
dc.typepl
JournalArticle
dspace.entity.type
Publication

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