Genome-wide meta-analysis identifies novel gender specific loci associated with thyroid antibodies level in Croatians

Genomics. 2019 Jul;111(4):737-743. doi: 10.1016/j.ygeno.2018.04.012. Epub 2018 Apr 18.


Autoimmune thyroid diseases (AITD) are multifactorial endocrine diseases most frequently accompanied by Tg and TPO autoantibodies. Both antibodies have a higher prevalence in females and act under a strong genetic influence. To identify novel variants underlying thyroid antibody levels, we performed GWAS meta-analysis on the plasma levels of TgAb and TPOAb in three Croatian cohorts, as well as gender specific GWAS and a bivariate analysis. No significant association was detected with the level of TgAb and TPOAb in the meta-analysis of GWAS or bivariate results for all individuals. The bivariate analysis in females only revealed a genome-wide significant association for the locus near GRIN3A (rs4457391, P = 7.76 × 10-9). The same locus had borderline association with TPOAb levels in females (rs1935377, P = 8.58 × 10-8). In conclusion, we identified a novel gender specific locus associated with TgAb and TPOAb levels. Our findings provide a novel insight into genetic and gender differences associated with thyroid antibodies.

Keywords: Genome-wide association study; Meta-analysis; Single nucleotide polymorphism; Thyroglobulin; Thyroid antibody; Thyroid peroxidase.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Calcium-Binding Proteins / genetics*
  • Croatia
  • Female
  • Humans
  • Iodide Peroxidase / immunology
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Sex Factors
  • Thyroglobulin / immunology
  • Thyroiditis, Autoimmune / genetics*


  • Autoantibodies
  • Calcium-Binding Proteins
  • DLK1 protein, human
  • GRIN3A protein, human
  • Membrane Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Thyroglobulin
  • Iodide Peroxidase