Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Nat Genet. 2023 Nov;55(11):1807-1819. doi: 10.1038/s41588-023-01520-w. Epub 2023 Oct 5.
A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
胎盘功能正常对于整个妊娠期间胎儿和母体的健康至关重要。我们使用胎盘重量作为胎盘生长的替代指标，对胎儿（n=65405）、母体（n=61228）和父体（n=52392）基因组进行了全基因组关联分析，得到了 40 个独立的关联信号。其中 26 个信号被归类为胎儿、4 个为母体、3 个为胎儿和母体。在 KCNQ1 附近观察到母体亲源效应。遗传相关性和共定位分析显示与出生体重遗传学存在重叠，但有 12 个位点被归类为主要或仅影响胎盘重量，与胎盘发育和形态以及抗体和氨基酸的转运有关。孟德尔随机化分析表明，胎儿遗传介导的较高胎盘重量与子痫前期风险和妊娠持续时间缩短有关。此外，这些分析支持胎儿胰岛素在调节胎盘重量中的作用，为胎儿和胎盘生长之间提供了关键联系。
