Genome-wide meta-analysis identifies novel loci associated with free triiodothyronine and thyroid-stimulating hormone.


Journal

Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594

Informations de publication

Date de publication:
Oct 2019
Historique:
received: 01 10 2018
accepted: 27 02 2019
pubmed: 8 3 2019
medline: 7 2 2020
entrez: 8 3 2019
Statut: ppublish

Résumé

Thyroid hormones are essential for the normal function of almost all human tissues, and have critical roles in metabolism, differentiation and growth. Free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels are under strong genetic influence; however, most of the heritability is yet unexplained. In order to identify novel loci associated with fT3, fT4 and TSH serum levels we performed a genome-wide meta-analysis of 7 411 206 polymorphisms in up to 1731 euthyroid individuals from three Croatian cohorts from Dalmatia region: two genetically isolated island populations and one mainland population. Additionally, we also performed a bivariate analysis of fT3 and fT4 levels. The EPHB2 gene variant rs67142165 reached genome-wide significance for association with fT3 plasma levels (P = 9.27 × 10 We identified a first genome-wide significant variant associated with fT3 plasma levels, as well as a novel locus associated with TSH plasma levels. These findings are biologically relevant and enrich our knowledge about the genetic basis of pituitary-thyroid axis function.

Identifiants

pubmed: 30843173
doi: 10.1007/s40618-019-01030-9
pii: 10.1007/s40618-019-01030-9
doi:

Substances chimiques

Triiodothyronine 06LU7C9H1V
Thyrotropin 9002-71-5

Types de publication

Journal Article Meta-Analysis

Langues

eng

Sous-ensembles de citation

IM

Pagination

1171-1180

Subventions

Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : Medical Research Council (UK), European Commission Framework 6 project EUROSPAN (Contract No.LSHG-CT-2006-018947), the Republic of Croatia Ministry of Science, Education and Sports research grant (216-1080315-0302), the Croatian Science Foundation (grant 8875), CEKOM (Ministry of Economy, Entrepreneurship and Crafts) and the Research Centre of Excellence in Personalized Medicine (Ministry of Science and Education)
ID : "10 001 Dalmatians" project
Organisme : Hrvatska Zaklada za Znanost
ID : 1498

Références

J Biol Chem. 2000 Jun 30;275(26):19803-7
pubmed: 10867024
Oncogene. 2000 Nov 20;19(49):5548-57
pubmed: 11114734
J Clin Endocrinol Metab. 2001 Mar;86(3):1206-11
pubmed: 11238510
Physiol Rev. 2001 Jul;81(3):1097-142
pubmed: 11427693
J Clin Endocrinol Metab. 2002 Mar;87(3):1068-72
pubmed: 11889165
Science. 2002 Dec 6;298(5600):1912-34
pubmed: 12471243
J Clin Endocrinol Metab. 2004 Mar;89(3):1181-7
pubmed: 15001606
J Clin Endocrinol Metab. 2005 Jul;90(7):4019-24
pubmed: 15870128
J Clin Endocrinol Metab. 2005 Sep;90(9):5317-20
pubmed: 15985488
Thyroid. 2006 Jan;16(1):73-8
pubmed: 16487017
Am J Physiol Endocrinol Metab. 2006 Jun;290(6):E1140-4
pubmed: 16682487
Am J Physiol Endocrinol Metab. 2007 Mar;292(3):E765-70
pubmed: 17090750
Eur J Endocrinol. 2007 Feb;156(2):181-6
pubmed: 17287407
Bioinformatics. 2007 May 15;23(10):1294-6
pubmed: 17384015
Oncogene. 2007 Oct 18;26(48):6905-14
pubmed: 17486069
Nat Genet. 2007 Jul;39(7):906-13
pubmed: 17572673
Clin Endocrinol (Oxf). 2008 Apr;68(4):652-9
pubmed: 17970774
Endocr Rev. 2008 Feb;29(1):76-131
pubmed: 17991805
Clin Biochem Rev. 2003 Nov;24(4):109-22
pubmed: 18568049
Croat Med J. 2009 Feb;50(1):4-6
pubmed: 19260138
Thyroid Res. 2009 Apr 02;2(1):4
pubmed: 19341475
Hum Reprod. 2009 Nov;24(11):2924-30
pubmed: 19654109
Bioinformatics. 2010 Sep 15;26(18):2336-7
pubmed: 20634204
Endocrinology. 2011 Mar;152(3):1154-64
pubmed: 21266507
Hum Genet. 2011 May;129(5):553-61
pubmed: 21274726
Nat Genet. 2011 Aug 14;43(9):897-901
pubmed: 21841780
BMC Genet. 2012 Jan 24;13:4
pubmed: 22272569
Adv Cancer Res. 2012;114:21-57
pubmed: 22588055
J Clin Endocrinol Metab. 2012 Aug;97(8):2724-31
pubmed: 22730515
J Obes. 2012;2012:926857
pubmed: 22811891
PLoS Genet. 2013;9(2):e1003266
pubmed: 23408906
Biomed Res Int. 2013;2013:725410
pubmed: 24282820
Expert Opin Drug Saf. 2014 Jun;13(6):723-33
pubmed: 24821006
Mol Cells. 2015 Jan 31;38(1):14-9
pubmed: 25475547
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Nat Commun. 2015 Mar 06;6:5681
pubmed: 25743335
Einstein (Sao Paulo). 2015 Jan-Mar;13(1):117-21
pubmed: 25807244
Oncotarget. 2016 May 10;7(19):28510-22
pubmed: 27058903
Thyroid. 2016 Oct;26(10):1441-1449
pubmed: 27599541
Lipids Health Dis. 2017 Jan 11;16(1):6
pubmed: 28077136
Best Pract Res Clin Endocrinol Metab. 2017 Mar;31(2):129-142
pubmed: 28648503
Nat Commun. 2017 Sep 6;8(1):447
pubmed: 28878392
Front Biosci (Landmark Ed). 2019 Jan 1;24:212-230
pubmed: 30468652
J Clin Endocrinol Metab. 1988 Jul;67(1):17-24
pubmed: 3379132
Clin Endocrinol (Oxf). 1993 Jul;39(1):101-7
pubmed: 8348700
Cancer Res. 1996 Mar 15;56(6):1184-8
pubmed: 8640794

Auteurs

M Popović (M)

Department of Medical Biology, University of Split, School of Medicine, Šoltanska 2, Split, Croatia.

A Matana (A)

Department of Medical Biology, University of Split, School of Medicine, Šoltanska 2, Split, Croatia.

V Torlak (V)

Department of Nuclear Medicine, University Hospital Split, Spinčićeva 1, Split, Croatia.

T Boutin (T)

MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, United Kingdom.

D Brdar (D)

Department of Nuclear Medicine, University Hospital Split, Spinčićeva 1, Split, Croatia.

I Gunjača (I)

Department of Medical Biology, University of Split, School of Medicine, Šoltanska 2, Split, Croatia.

D Kaličanin (D)

Department of Medical Biology, University of Split, School of Medicine, Šoltanska 2, Split, Croatia.

I Kolčić (I)

Department of Public Health, University of Split, School of Medicine Split, Šoltanska 2, Split, Croatia.

V Boraska Perica (V)

Department of Medical Biology, University of Split, School of Medicine, Šoltanska 2, Split, Croatia.

A Punda (A)

Department of Nuclear Medicine, University Hospital Split, Spinčićeva 1, Split, Croatia.

O Polašek (O)

Department of Public Health, University of Split, School of Medicine Split, Šoltanska 2, Split, Croatia.

M Barbalić (M)

Department of Medical Biology, University of Split, School of Medicine, Šoltanska 2, Split, Croatia.

C Hayward (C)

MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, United Kingdom.

T Zemunik (T)

Department of Medical Biology, University of Split, School of Medicine, Šoltanska 2, Split, Croatia. tzemunik@mefst.hr.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH