Endocrine Abstracts (2016) 41 OC8.3 | DOI: 10.1530/endoabs.41.OC8.3

Identification of novel genetic loci associated with thyroid function

Dubravka Brdar1, Antonela Boljat2, Vesela Torlak1, Ante Punda1, Vesna Boraska2, Ivana Gunjaca2, Nikolina Vidan2, Bernarda Lozic3, Ozren Polasek4, Caroline Hayward5, Maja Barbalic2 & Tatijana Zemunik2


1Department of Nuclear Medicine, University Hospital Split, Split, Croatia; 2Department of Medical Biology, University of Split, School of Medicine, Split, Croatia; 3Department of Pediatrics, University Hospital Split, Split, Croatia; 4Department of Epidemiology, University of Split, School of Medicine Split, Split, Croatia; 5MRC Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK.


Objective: Thyroid hormones have essential role in regulation of cellular growth, development and metabolism. Although genetic variants seem to be an important determinant of thyroid hormone levels the data about involved genes are still limited. Therefore, in order to determine genetic variants underlying thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) plasma level we performed a genome wide association study (GWAS) in Croatian subjects.

Methods: Immunoassay method was used to determine circulating plasma level of TSH, fT4 and fT3 in 1012 participants from Split, Croatia. Participants with a history of thyroid disease treatment (41 of them) were excluded from the study. The GWAS for TSH, fT4 and fT3 was performed using 1000 genomes imputed data and was accounted for genetic relatedness among individuals. Association was tested by linear regression adjusted for sex and age assuming an additive genetic model.

Results: We identified one new locus associated with fT3 level with genome-wide significance: rs118173732 located upstream of DIAPH3 gene on the 13q21.2 (P=4.9059359×10−8; β=−1.2195316; SE=−0.2235750).

Conclusion: The study found new locus associated with fT3 level in general population. The results should be checked in a replication study.