University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia.
Int J Obes (Lond). 2018 Apr;42(4):775-784. doi: 10.1038/ijo.2017.248. Epub 2017 Oct 9.
Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.
A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).
Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.
We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.
临床建议限制妊娠体重增加（GWG）意味着高 GWG 与母婴不良结局有因果关系，但 GWG 是几个相互关联的复杂表型（母体脂肪沉积和血管扩张、胎盘、羊水和胎儿生长）的总和。了解 GWG 的遗传贡献有助于阐明其不同成分对母婴健康的潜在影响。本研究旨在探讨 GWG 总量、早期和晚期 GWG 的遗传贡献。
使用全基因组关联研究来鉴定多达 10543 名欧洲裔母亲和 16317 名后代的 GWG 相关的母体和胎儿变异，在 10660 名母亲和 7561 名后代中进行了复制。额外的分析确定了 GWG 中母体和胎儿常见遗传变异的变异性比例，以及与 GWG 相关的已建立的全基因组显著变异（例如，母体体重指数（BMI）和葡萄糖、出生体重）的重叠。
GWG 变异的约 20%由常见的母体遗传变异标记，胎儿基因组对 GWG 变异的解释作用微不足道。在后代基因组中，妊娠特异性β-1 糖蛋白 5（PSG5）基因附近的变异与 GWG 总量达到全基因组显著水平（P=1.71×10），但未复制。一些与 BMI、空腹血糖和 2 型糖尿病增加相关的已建立变异与早期 GWG 降低和晚期 GWG 升高有关。与收缩压升高相关的母体变异与晚期 GWG 降低有关。与母体和胎儿出生体重相关的已建立变异与 GWG 关系不大。
我们发现母体常见变异对 GWG 有适度贡献，一些母体 BMI、葡萄糖和 2 型糖尿病变异与 GWG 重叠。这些发现表明，GWG 与后代/母体结局的关联可能是由于母体 BMI 和糖尿病与 GWG 的关系。
