Uncovering the shared genetic components of thyroid disorders and reproductive health

Abstract

Abstract Objective The aim of the study is to map the shared genetic component and relationships between thyroid and reproductive health traits to improve the understanding of the interplay between those domains. Design 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. Methods We evaluated genetic associations using genome-wide association study (GWAS) meta-analysis, GWAS Catalog lookup, gene prioritization, mouse phenotype lookup, and genetic correlation analysis. Results GWAS meta-analysis results for thyroid phenotypes showed that 50 lead variants out of 253 (including 5/52 of the novel hits) were linked to reproductive health in previous literature. Genetic correlation analyses revealed significant correlations between hypothyroidism and reproductive phenotypes. The results showed that 31.9% of thyroid-associated genes also had an impact on reproductive phenotypes, with the most affected functions being related to genitourinary tract issues. Conclusions The study discovers novel genetic loci linked to thyroid phenotypes and highlights the shared genetic determinants between thyroid function and reproductive health, providing evidence for the genetic pleiotropy and shared biological mechanisms between these traits in both sexes.