Fuentes-Paez Georgina, Escaramís Geòrgia, Aguilar-Lacasaña Sofía, Andrusaityte Sandra, Brantsæter Anne Lise, Casas Maribel, Charles Marie-Aline, Chatzi Leda, Lepeule Johanna, Grazuleviciene Regina, Gützkow Kristine B, Heude Barbara, Maitre Léa, Ruiz-Arenas Carlos, Sunyer Jordi, Urquiza Jose, Yang Tiffany C, Wright John, Vrijheid Martine, Vilor-Tejedor Natàlia, Bustamante Mariona
Endocrine Regulatory Genomics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain.
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
Front Genet. 2022 May 12;13:867611. doi: 10.3389/fgene.2022.867611. eCollection 2022.
Maternal smoking during pregnancy has adverse health effects on the offspring, including lower birth weight and increased risk for obesity. These outcomes are also influenced by common genetic polymorphisms. We aimed to investigate the combined effect of maternal smoking during pregnancy and genetic predisposition on birth weight and body mass index (BMI)-related traits in 1,086 children of the Human Early Life Exposome (HELIX) project. Maternal smoking during pregnancy was self-reported. Phenotypic traits were assessed at birth or at the age of 8 years. Ten polygenic risk scores (PRSs) per trait were calculated using the PRSice v2 program. For birth weight, we estimated two sets of PRSs based on two different base GWAS summary statistics: PRS-EGG, which includes HELIX children, and PRS-PanUK, which is completely independent. The best PRS per trait (highest ) was selected for downstream analyses, and it was treated in continuous or categorized into three groups. Multivariate linear regression models were applied to evaluate the association of the explanatory variables with the traits of interest. The combined effect was evaluated by including an interaction term in the regression models and then running models stratified by the PRS group. BMI-related traits were correlated among them but not with birth weight. A similar pattern was observed for their PRSs. On average, the PRSs explained ∼4% of the phenotypic variation, with higher PRS values related to higher trait values (-value <5.55E-08). Sustained maternal smoking was associated with lower birth weight and higher BMI and related traits (-value <2.99E-02). We identified a gene by environment (GxE) interaction for birth weight between sustained maternal smoking and the PRS-EGG in three groups (-value interaction = 0.01), which was not replicated with the PRS-PanUK (-value interaction = 0.341). Finally, we did not find any statistically significant GxE interaction for BMI-related traits (-value interaction >0.237). Sustained maternal smoking and the PRSs were independently associated with birth weight and childhood BMI-related traits. There was low evidence of GxE interactions.
孕期母亲吸烟会对后代健康产生不良影响，包括出生体重较低以及肥胖风险增加。这些结果也受到常见基因多态性的影响。我们旨在研究孕期母亲吸烟与遗传易感性对人类早期生活暴露组（HELIX）项目中1086名儿童出生体重和体重指数（BMI）相关性状的综合影响。孕期母亲吸烟情况通过自我报告获得。表型性状在出生时或8岁时进行评估。使用PRSice v2程序为每个性状计算了10个多基因风险评分（PRS）。对于出生体重，我们基于两组不同的全基因组关联研究（GWAS）汇总统计数据估计了两组PRS：包括HELIX儿童的PRS-EGG，以及完全独立的PRS-PanUK。为下游分析选择每个性状的最佳PRS（最高 ），并将其视为连续变量或分为三组。应用多元线性回归模型来评估解释变量与感兴趣性状之间的关联。通过在回归模型中纳入交互项，然后按PRS组进行分层运行模型来评估综合效应。BMI相关性状之间相互关联，但与出生体重无关。它们的PRS也观察到类似模式。平均而言，PRS解释了约4%的表型变异，较高的PRS值与较高的性状值相关（-值<5.55E-08）。持续的孕期母亲吸烟与较低的出生体重、较高的BMI及相关性状有关（-值<2.99E-02）。我们在三组中发现了持续孕期母亲吸烟与PRS-EGG之间出生体重的基因与环境（GxE）交互作用（-值交互作用=0.01），而在PRS-PanUK中未得到重复（-值交互作用=0.341）。最后，我们未发现BMI相关性状有任何统计学上显著的GxE交互作用（-值交互作用>0.237）。持续的孕期母亲吸烟和PRS与出生体重及儿童期BMI相关性状独立相关。GxE交互作用的证据较少。
