Common maternal and fetal genetic variants show expected polygenic effects on risk of small- or large-for-gestational-age (SGA or LGA), except in the smallest 3% of babies.
Common maternal and fetal genetic variants show expected polygenic effects on risk of small- or large-for-gestational-age (SGA or LGA), except in the smallest 3% of babies.
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DOI：
10.1371/journal.pgen.1009191
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发表时间：
2020-12
期刊：
影响因子：
4.5
通讯作者：
Kotecha S
中科院分区：
文献类型：
--
作者：
Beaumont RN;Kotecha SJ;Wood AR;Knight BA;Sebert S;McCarthy MI;Hattersley AT;Järvelin MR;Timpson NJ;Freathy RM;Kotecha S
临床上出生的婴儿小于或大于胎龄（SGA或LGA;分别为性别和胎龄调整的出生体重（BW）<10th or >第90百分位数），并发症的风险更高。SGA和LGA分别包括经历过与环境相关的生长受限或过度生长的婴儿，以及遗传性矮小或高大的婴儿。然而，各组内的相对比例尚不清楚。我们评估了导致出生体重变异的常见遗传变异对SGA或LGA概率的影响程度。我们计算了11，951名婴儿和5，182名母亲的BW的独立胎儿和母亲遗传评分（GS）。这些评分分别反映了胎儿和母体（通过宫内环境）对BW的直接遗传贡献。计算孕妇空腹血糖（FG）和收缩压（SBP）GS。我们测试了每个GS和SGA或LGA概率之间的关联。对于BW GS，我们使用模拟来评估偏离预期多基因模型的证据。高体重GS与低SGA和高LGA的几率密切相关（OR胎儿= 0.75（0.71，0.80）和1.32（1.26，1.39）; OR母体= 0.81（0.75，0.88）和1.17（1.09，1.25），每增加十分位GS）。我们发现，有证据表明，最小的3%的婴儿有一个更高的BW GS，平均而言，比预期从他们的观察出生体重（假设一个加性多基因模型：P胎儿= 0.014，P产妇= 0.062）。较高的母体SBP GS与较高的SGA几率相关，P = 0.005。我们的结论是，常见的遗传变异有助于SGA和LGA的风险，但在最小的3%的婴儿中，其他因素对SGA的风险变得更加重要。对于给定胎龄，出生体重（BW）在人口分布中最低或最高10%的婴儿分别被称为小于或大于胎龄（SGA或LGA）。与体重接近平均水平的婴儿相比，这些婴儿患并发症的风险更高。SGA和LGA婴儿可能分别经历了生长受限或过度生长，但也可能只是处于正常生长分布的末端。这些组中正常与次优生长的相对比例尚不清楚。为了研究常见遗传变异在SGA和LGA中的作用，我们在11，951名欧洲血统个体中测试了它们与BW胎儿遗传评分（GS）的相关性。我们还测试了与母体GS（5，182位母亲）的后代BW，空腹血糖和收缩压的相关性，每一项都通过子宫内环境影响胎儿生长。我们发现胎儿和母体GS与SGA和LGA相关，支持母体和胎儿对出生体重的强遗传贡献。然而，在最小的3%的婴儿中，母体和胎儿的体重GS高于预期，这表明除了常见的遗传变异之外，其他因素在决定这些非常小的婴儿的出生体重方面更重要。
Babies born clinically Small- or Large-for-Gestational-Age (SGA or LGA; sex- and gestational age-adjusted birth weight (BW) <10th or >90th percentile, respectively), are at higher risks of complications. SGA and LGA include babies who have experienced environment-related growth-restriction or overgrowth, respectively, and babies who are heritably small or large. However, the relative proportions within each group are unclear. We assessed the extent to which common genetic variants underlying variation in birth weight influence the probability of being SGA or LGA. We calculated independent fetal and maternal genetic scores (GS) for BW in 11,951 babies and 5,182 mothers. These scores capture the direct fetal and indirect maternal (via intrauterine environment) genetic contributions to BW, respectively. We also calculated maternal fasting glucose (FG) and systolic blood pressure (SBP) GS. We tested associations between each GS and probability of SGA or LGA. For the BW GS, we used simulations to assess evidence of deviation from an expected polygenic model. Higher BW GS were strongly associated with lower odds of SGA and higher odds of LGA (ORfetal = 0.75 (0.71,0.80) and 1.32 (1.26,1.39); ORmaternal = 0.81 (0.75,0.88) and 1.17 (1.09,1.25), respectively per 1 decile higher GS). We found evidence that the smallest 3% of babies had a higher BW GS, on average, than expected from their observed birth weight (assuming an additive polygenic model: Pfetal = 0.014, Pmaternal = 0.062). Higher maternal SBP GS was associated with higher odds of SGA P = 0.005. We conclude that common genetic variants contribute to risk of SGA and LGA, but that additional factors become more important for risk of SGA in the smallest 3% of babies. Babies in the lowest or highest 10% of the population distribution of birth weight (BW) for a given gestational age are referred to as Small- or Large-for-Gestational-Age (SGA or LGA) respectively. These babies have higher risks of complications compared with babies with BW closer to the average. SGA and LGA babies may have experienced growth restriction or overgrowth, respectively, but may alternatively just be at the tail ends of the normal growth distribution. The relative proportions of normal vs. sub-optimal growth within these groups is unclear. To examine the role of common genetic variation in SGA and LGA, we tested their associations with a fetal genetic score (GS) for BW in 11,951 European-ancestry individuals. We also tested associations with maternal GS (5,182 mothers) for offspring BW, fasting glucose and systolic blood pressure, each of which influences fetal growth via the in utero environment. We found fetal and maternal GS were associated with SGA and LGA, supporting strong maternal and fetal genetic contributions to birth weight in both tails of the distribution. However, within the smallest 3% of babies, the maternal and fetal GS for BW were higher than expected, suggesting factors additional to common genetic variation are more important in determining birth weight in these very small babies.
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影响因子：
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DOI：
10.1016/0002-9378(93)90491-z
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1993-02-01
影响因子：
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