Genome Wide Association Study of Serum Levels of Thyroid Hormones in Qatari Population

Abstract

Thyroid gland is a major part of the endocrine system, it maintains the energy and metabolism balance in the human body. In addition to environmental factors, genetics also contribute to thyroid function and the hormones levels. GWAS studies has provided a tool to identify genetic variants associated with thyroid function traits, thus provide an insight into the genetic architecture of thyroid gland. GWAS has been extensively implemented in European population and since frequency of alleles and variants effect size differ across populations; this study, is applied to the unique Qatari population. Here, we aim to conduct genome wide association analysis using whole genome sequence data to detect genotype associations with three serum thyroid hormones: TSH, free T3, and free T4. The discovery stage analysis was performed on 6,047 subjects, and further replicating the results in another set of subjects (n=7,768) form the same cohort (Qatar Biobank). For TSH serum levels, we replicated eight loci previously reported in GWAS of European population: CAPZB, NFIA, AC007563.2, AC002460.2, VAV3, PDE10A, PDE8B and INSR. Three loci replicated for free T4 levels: DIO1, NRK, and SERPINA7. Associated variants with free T3 are novel findings of this study: DIO1, PTCSC2, SERPINA7, LINC00378 and MIR3169. In addition to five novel loci for serum free T4: EEFSEC, MCHR2-AS1, RNU6-99P (snRNA), BMF (mRNA), and LINC00536 (lncRNA). The direction of effect size for the replicated loci was same in comparison to other populations. However, some variants were higher in frequency in Qatari population compared to Europeans, highlighting the existence of population specific variants. Further functional studies for the identified variants are needed to investigate the impact of genetic variants on the thyroid function and advance our understanding on molecular pathways involved in regulating Thyroid hormones.

Date of Award	2021
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences