Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA.
Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, USA.
Sci Rep. 2023 Jan 6;13(1):322. doi: 10.1038/s41598-022-26572-6.
The placenta is critical to human growth and development and has been implicated in health outcomes. Understanding the mechanisms through which the placenta influences perinatal and later-life outcomes requires further investigation. We evaluated the relationships between birthweight and adult body mass index (BMI) and genetically-predicted gene expression in human placenta. Birthweight genome-wide association summary statistics were obtained from the Early Growth Genetics Consortium (N = 298,142). Adult BMI summary statistics were obtained from the GIANT consortium (N = 681,275). We used S-PrediXcan to evaluate associations between the outcomes and predicted gene expression in placental tissue and, to identify genes where placental expression was exclusively associated with the outcomes, compared to 48 other tissues (GTEx v7). We identified 24 genes where predicted placental expression was significantly associated with birthweight, 15 of which were not associated with birthweight in any other tissue. One of these genes has been previously linked to birthweight. Analyses identified 182 genes where placental expression was associated with adult BMI, 110 were not associated with BMI in any other tissue. Eleven genes that had placental gene expression levels exclusively associated with BMI have been previously associated with BMI. Expression of a single gene, PAX4, was associated with both outcomes exclusively in the placenta. Inter-individual variation of gene expression in placental tissue may contribute to observed variation in birthweight and adult BMI, supporting developmental origins hypothesis.
胎盘对于人类的生长和发育至关重要，并与健康结果有关。为了深入了解胎盘影响围产期和后期生命结果的机制，我们需要进一步研究。我们评估了胎盘基因表达与出生体重和成人 BMI 之间的关系。出生体重的全基因组关联汇总统计数据来自早期生长遗传学联盟（N=298142）。成人 BMI 汇总统计数据来自 GIANT 联盟（N=681275）。我们使用 S-PrediXcan 来评估这些结果与胎盘组织中预测基因表达之间的关联，并鉴定出与其他 48 种组织（GTEx v7）相比，仅与这些结果相关的胎盘表达的基因。我们鉴定出 24 个与出生体重显著相关的预测胎盘表达基因，其中 15 个在其他任何组织中均与出生体重无关。其中一个基因之前与出生体重有关。分析还鉴定出 182 个与成人 BMI 相关的胎盘表达基因，其中 110 个在其他任何组织中均与 BMI 无关。有 11 个与 BMI 相关的基因，其胎盘基因表达水平仅与 BMI 相关，这些基因之前也与 BMI 有关。单个基因 PAX4 的表达仅在胎盘组织中与这两个结果相关。胎盘组织中基因表达的个体间变异可能导致观察到的出生体重和成人 BMI 的差异，这支持了发育起源假说。
