Genome-wide association studies of thyroid-related hormones, dysfunction, and autoimmunity among 85,421 Chinese pregnancies

• Published in: Nature communications Vol. 15; no. 1; pp. 8004 - 17
• Main Authors: Wei, Yuandan, Zhen, Jianxin, Hu, Liang, Gu, Yuqin, Liu, Yanhong, Guo, Xinxin, Yang, Zijing, Zheng, Hao, Cheng, Shiyao, Wei, Fengxiang, Xiong, Likuan, Liu, Siyang
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 13.09.2024; Nature Portfolio
• Subjects: Adult; Asian People - genetics; Autoantibodies - blood; Autoantibodies - immunology; Autoimmunity; Autoimmunity - genetics; Blood levels; Blood pressure; China - epidemiology; East Asian People; Epidemiology; Female; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Hormones; Humans; Iodide peroxidase; Iodide Peroxidase - genetics; Iodide Peroxidase - immunology; Mendelian Randomization Analysis; Peroxidase; Phenotypes; Polymorphism, Single Nucleotide; Pregnancy; Pregnancy Complications - epidemiology; Pregnancy Complications - genetics; Pregnancy Complications - immunology; Thyroid; Thyroid Diseases - epidemiology; Thyroid Diseases - genetics; Thyroid Diseases - immunology; Thyroid gland; Thyroid Gland - immunology; Thyroid Hormones - blood; Thyroid-stimulating hormone; Thyrotropin - blood; Womens health; China
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-52236-2

Maintaining normal thyroid function is crucial in pregnancy, yet thyroid dysfunction and the presence of thyroid peroxidase antibodies (TPOAb) affect 0.5% to 18% of pregnant women. Here, we conducted a genome-wide association study (GWAS) of eight thyroid traits, including two thyroid-related hormones, four thyroid dysfunctions, and two thyroid autoimmunity measurements among 85,421 Chinese pregnant women to investigate the genetic basis of thyroid function during pregnancy. Our study identified 176 genetic loci, including 125 previously unknown genome-wide associations. Joint epidemiological and Mendelian randomization analyses revealed significant associations between the gestational thyroid phenotypes and gestational complications, birth outcomes, and later-age health outcomes. Specifically, genetically elevated thyroid-stimulating hormone (TSH) levels during pregnancy correlated with lower glycemic levels, reduced blood pressure, and longer gestational duration. Additionally, TPOAb and thyroid functions during pregnancy share genetic correlations with later-age thyroid and cardiac disorders. These findings provide insights into the genetic determinants of thyroid traits during pregnancy, which may lead to new therapeutics, early pre-diagnosis and preventive strategies starting from early adulthood.