Dpt. of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynaecology, and Reproductology, 199034 St. Petersburg, Russia.
Faculty of Software Engineering and Computer Systems, ITMO University, 197101 St. Petersburg, Russia.
Genes (Basel). 2022 Nov 30;13(12):2255. doi: 10.3390/genes13122255.
Complications endangering mother or fetus affect around one in seven pregnant women. Investigation of the genetic susceptibility to such diseases is of high importance for better understanding of the disease biology as well as for prediction of individual risk. In this study, we collected and analyzed GWAS summary statistics from the FinnGen cohort and UK Biobank for 24 pregnancy complications. In FinnGen, we identified 11 loci associated with pregnancy hypertension, excessive vomiting, and gestational diabetes. When UK Biobank and FinnGen data were combined, we discovered six loci reaching genome-wide significance in the meta-analysis. These include rs35954793 in (p=6.1×10-9), rs10882398 in (p=8.9×10-9), and rs167479 in (p=5.2×10-9) for pregnancy hypertension, rs10830963 in (p=4.5×10-41) and rs36090025 in (p=3.4×10-15) for gestational diabetes, and rs2963457 in the locus (p=6.5×10-9) for preterm birth. In addition to the identified genome-wide associations, we also replicated 14 out of 40 previously reported GWAS markers for pregnancy complications, including four more preeclampsia-related variants. Finally, annotation of the GWAS results identified a causal relationship between gene expression in the cervix and gestational hypertension, as well as both known and previously uncharacterized genetic correlations between pregnancy complications and other traits. These results suggest new prospects for research into the etiology and pathogenesis of pregnancy complications, as well as early risk prediction for these disorders.
影响约七分之一孕妇的危及母婴健康的并发症。对这些疾病的遗传易感性进行研究对于更好地了解疾病生物学以及预测个体风险非常重要。在这项研究中，我们收集并分析了 FinnGen 队列和 UK Biobank 中 24 种妊娠并发症的 GWAS 汇总统计数据。在 FinnGen 中，我们确定了 11 个与妊娠高血压、过度呕吐和妊娠糖尿病相关的位点。当 UK Biobank 和 FinnGen 数据合并时，我们在荟萃分析中发现了六个达到全基因组显著水平的位点。这些包括位于 （p=6.1×10-9）的 rs35954793、位于 （p=8.9×10-9）的 rs10882398 和位于 （p=5.2×10-9）的 rs167479、位于 （p=4.5×10-41）的 rs10830963、位于 （p=3.4×10-15）的 rs36090025 与妊娠高血压相关，位于 （p=6.5×10-9）的 rs2963457 与早产相关。除了确定的全基因组关联外，我们还复制了 40 个先前报道的妊娠并发症 GWAS 标记中的 14 个，包括四个与子痫前期相关的变体。最后，GWAS 结果的注释确定了宫颈基因表达与妊娠高血压之间的因果关系，以及妊娠并发症与其他特征之间已知和以前未描述的遗传相关性。这些结果为妊娠并发症的病因和发病机制研究以及这些疾病的早期风险预测提供了新的前景。
