School of Psychological Science, University of Bristol, Bristol, UK.
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
BMC Res Notes. 2023 Jul 30;16(1):159. doi: 10.1186/s13104-023-06438-4.
To use genome-wide association study (GWAS) by subtraction, a method for deriving novel GWASs from existing summary statistics, to derive genome-wide summary statistics for paternal smoking.
A GWAS by subtraction was implemented using a weighted linear model that defined the child-genotype paternal-phenotype association as the child-genotype child-phenotype association minus the child-genotype maternal-phenotype association. We first use the laws of inherence to derive the weighted linear model. We then implemented the linear model to create a GWAS of paternal smoking by subtracting the summary statistics from a GWAS of maternal smoking from the summary statistics of a GWAS of the index individual's smoking. We used a Monte-Carlo simulation to validate the model and showed that this approach performed similarly in terms of bias to performing a traditional GWAS of paternal smoking. Finally, we validated the summary statistics in a Mendelian randomisation analysis by demonstrating an association of genetically predicted paternal smoking with paternal lung cancer and emphysema.
利用基于减法的全基因组关联研究（GWAS），即从现有汇总统计数据中推导出新 GWAS 的方法，推导出与父系吸烟有关的全基因组汇总统计数据。
使用加权线性模型实施基于减法的 GWAS，该模型将儿童基因型与父系表型的关联定义为儿童基因型与儿童表型的关联减去儿童基因型与母系表型的关联。我们首先使用遗传规律推导出加权线性模型。然后，我们通过从母系吸烟的 GWAS 汇总统计数据中减去索引个体吸烟的 GWAS 汇总统计数据，实施线性模型来创建父系吸烟的 GWAS 减法。我们使用蒙特卡罗模拟验证了该模型，并表明该方法在偏倚方面与传统的父系吸烟 GWAS 相似。最后，我们通过证明遗传预测的父系吸烟与父系肺癌和肺气肿之间存在关联，在孟德尔随机化分析中验证了汇总统计数据。
