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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. Normal maternal thyroid function holds significant relevance for pregnancy outcomes and long-term health. Here, the authors detect genetic associations with thyroid related traits in pregnant women. [ABSTRACT FROM AUTHOR]

Metabolites are key indicators of health and therapeutic targets, but their genetic underpinnings during pregnancy-a critical period for human reproduction-are largely unexplored. Using genetic data from non-invasive prenatal testing, we performed a genome-wide association study on 84 metabolites, including 37 amino acids, 24 elements, 13 hormones, and 10 vitamins, involving 34,394 pregnant Chinese women, with sample sizes ranging from 6,394 to 13,392 for specific metabolites. We identified 53 metabolite-gene associations, 23 of which are novel. Significant differences in genetic effects between pregnant and non-pregnant women were observed for 16.7%-100% of these associations, indicating gene-environment interactions. Additionally, 50.94% of genetic associations exhibited pleiotropy among metabolites and between six metabolites and eight pregnancy phenotypes. Mendelian randomization revealed potential causal relationships between seven maternal metabolites and 15 human traits and diseases. These findings provide new insights into the genetic basis of maternal plasma metabolites during pregnancy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To explore the role of inhibitory KIR (iKIR) and its cognate HLA ligand in the occurrence and development of cervical cancer among ethnic Han Chinese and its potential mechanism., Methods: Peripheral blood samples from 265 Han Chinese patients with cervical intraepithelial neoplasia (CIN)/cervical cancer and 200 ethnically matched healthy controls were collected. The results of KIR PCR-SSP, HLA PCR-rSSO and KIR3DL1 PCR-SBT, together with cervical cancer data from the TCGA database, were used to assess the association of iKIR genes, receptor-ligand gene combinations, iKIR transcription level in the tumor tissue and the KIR3DL1 alleles with the occurrence and development of cervical cancer., Results: Among the four iKIR genes (KIR2DL1, 2DL2/3, 3DL1 and 3DL2), the frequencies of KIR3DL1 and KIR3DL1-HLA-Bw4 genes among controls were significantly higher than those of the cervical cancer group (96.5% vs. 87.0%, P = 0.018; 81.5% vs. 64.8%, P=0.009). The survival rate of cervical cancer patients with a high transcription level of KIR3DL1 in tumor tissues was significantly higher than those with a low/medium transcription level (P=0.028). The frequency of strong-inhibitory and high-expression KIR3DL1*01502 allele among the healthy population was significantly higher than that of the cervical cancer group (76.0% vs. 59.3%, P =0.015)., Conclusion: Combined KIR3DL1 and KIR3DL1-HLA-Bw4 can confer a protective effect against the development of cervical cancer, which may be attributed to the strong-inhibitory and high-expression allele of KIR3DL1*01502.