Uncovering the Shared Genetic Components of Thyroid Disorders and Reproductive Health
Jéssica FiguerêdoiD, Kristi KrebsiD, Natàlia Pujol‐GualdoiD, Toomas HalleriD, Urmo VõsaiD, Vallo VolkeiD, Triin LaiskiD, Reedik MägiiD, Andres MetspaluiD, Lili A. MilaniiD, Tõnu EskoiD, Mari NelisiD, Georgi HudjashoviD, Raivo KoldeiD, Sven LauriD, Sulev ReisbergiD, Jaak ViloiD
Abstract
Thyroid disorders are complex and polygenic, and thus result from the interaction of many genetic variants. Due to a central role of the thyroid hormones in the body, their dysfunction can have a significant impact on the reproductive health in men and women. Mapping the shared genetic component and relationships between thyroid and reproductive health traits will improve the understanding about the interplay between those domains. Here, a large-scale genetic analysis of thyroid traits (hyper- and hypothyroidism, and thyroid stimulating hormone levels) was conducted in up to 743,088 individuals of European ancestry from various cohorts. We evaluated genetic and phenotypic associations using genome-wide association study (GWAS) meta-analysis, gene prioritisation, genetic correlation analysis, and phenotype vs phenome-wide-association analysis. The results showed that 32% of thyroid-associated genes also had an impact on reproductive phenotypes, with the most affected functions being related to genitourinary tract issues. The study highlights the shared genetic determinants between thyroid function and reproductive health, providing evidence for the genetic pleiotropy between these traits in both men and women.
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