评估遗传评分在添加到临床和人体测量指标后是否能解释出生体重的额外变异。

Assessing whether genetic scores explain extra variation in birthweight, when added to clinical and anthropometric measures.

机构信息

Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Barrack Road, Exeter, Devon, EX2 5DW, UK.

NIHR Exeter Clinical Research Facility, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.

出版信息

BMC Pediatr. 2022 Aug 25;22(1):504. doi: 10.1186/s12887-022-03554-1.

DOI:10.1186/s12887-022-03554-1

PMID:36008798

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9414111/

Abstract

BACKGROUND

Human birthweight is a complex, multifactorial trait. Maternal characteristics contribute to birthweight variation by influencing the intrauterine environment. Variation explained by genetic effects is also important, but their contributions have not been assessed alongside other key determinants. We aimed to investigate variance in birthweight explained by genetic scores in addition to easily-measurable clinical and anthropometric variables.

METHODS

We analysed 549 European-ancestry parent-offspring trios from a UK community-based birth cohort. We investigated variance explained in birthweight (adjusted for sex and gestational age) in multivariable linear regression models including genetic scores, routinely-measured maternal characteristics, and parental anthropometric variables. We used R-Squared (R) to estimate variance explained, adjusted R-squared (Adj-R) to assess improvement in model fit from added predictors, and F-tests to compare nested models.

RESULTS

Maternal and fetal genetic scores together explained 6.0% variance in birthweight. A model containing maternal age, weight, smoking, parity and 28-week fasting glucose explained 21.7% variance. Maternal genetic score explained additional variance when added to maternal characteristics (Adj-R = 0.233 vs Adj-R = 0.210, p < 0.001). Fetal genetic score improved variance explained (Adj-R = 0.264 vs 0.248, p < 0.001) when added to maternal characteristics and parental heights.

CONCLUSIONS

Genetic scores account for variance explained in birthweight in addition to easily measurable clinical variables. Parental heights partially capture fetal genotype and its contribution to birthweight, but genetic scores explain additional variance. While the genetic contribution is modest, it is comparable to that of individual clinical characteristics such as parity, which suggests that genetics could be included in tools aiming to predict risk of high or low birthweights.

摘要

背景

人类的出生体重是一种复杂的多因素特征。母体特征通过影响宫内环境对出生体重的变化产生影响。遗传效应解释的变异性也很重要，但它们的贡献尚未与其他关键决定因素一起评估。我们旨在调查除了易于测量的临床和人体测量变量之外，遗传评分对出生体重的变异解释。

方法

我们分析了来自英国社区为基础的出生队列的 549 个欧洲血统的父母-子女三胞胎。我们在多变量线性回归模型中调查了出生体重（调整性别和胎龄）的变异解释，包括遗传评分、常规测量的母体特征和父母的人体测量变量。我们使用 R 平方（R）来估计变异解释，调整后的 R 平方（Adj-R）来评估增加预测因子后的模型拟合度提高，以及 F 检验来比较嵌套模型。

结果

母体和胎儿的遗传评分共同解释了出生体重的 6.0%的变异。包含母亲年龄、体重、吸烟、产次和 28 周空腹血糖的模型解释了 21.7%的变异。当添加到母体特征时，母体遗传评分解释了额外的变异（Adj-R=0.233 比 Adj-R=0.210，p<0.001）。当添加到母体特征和父母身高时，胎儿遗传评分提高了变异解释（Adj-R=0.264 比 0.248，p<0.001）。