We investigate the impact of confounding on the results of a genome-wide association analysis by Beaty et al., which identified multiple single nucleotide polymorphisms that appeared to modify the effect of maternal smoking, alcohol consumption, or multivitamin supplementation on risk of cleft palate. The study sample of case-parent trios was primarily of European and East Asian ancestry, and the distribution of all three exposures differed by ancestral group. Such differences raise the possibility that confounders, rather than the exposures, are the risk modifiers and hence that the inference of gene-environment (G×E) interaction may be spurious. Our analyses generally confirmed the result of Beaty et al. and suggest the interaction G×E is driven by the European trios, whereas the East Asian trios were less informative.

我们研究了混淆对Beaty等人进行的全基因组关联分析结果的影响，该分析确定了多个单核苷酸多态性，这些多态性似乎可以改变孕妇吸烟，饮酒或补充多种维生素对c裂风险的影响。个案-父母三人组的研究样本主要来自欧洲和东亚血统，并且所有三种暴露的分布因祖先组而异。这样的差异增加了混杂因素而不是暴露因素是风险修饰因子的可能性，因此推论了基因环境（G×Ë）互动可能是虚假的。我们的分析总体上证实了Beaty等人的结果。并建议互动G×Ë 由欧洲三重奏驱动，而东亚三重奏的信息量较少。