Walsh Ryan, Voorhies Kirsten, McDonald Merry-Lynn, McGeachie Michael, Sordillo Joanne E, Lange Christoph, Wu Ann Chen, Lutz Sharon M
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA 02215, USA.
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J Pers Med. 2021 Feb 19;11(2):145. doi: 10.3390/jpm11020145.
Genome-wide association studies (GWAS) play a critical role in identifying many loci for common diseases and traits. There has been a rapid increase in the number of GWAS over the past decade. As additional GWAS are being conducted, it is unclear whether a novel signal associated with the trait of interest is independent of single nucleotide polymorphisms (SNPs) in the same region that has been previously associated with the trait of interest. The general approach to determining whether the novel association is independent of previous signals is to examine the association of the novel SNP with the trait of interest conditional on the previously identified SNP and/or calculate linkage disequilibrium (LD) between the two SNPs. However, the role of epistasis and SNP by SNP interactions are rarely considered. Through simulation studies, we examined the role of SNP by SNP interactions when determining the independence of two genetic association signals. We have created an R package on Github called gxgRC to generate these simulation studies based on user input. In genetic association studies of asthma, we considered the role of SNP by SNP interactions when determining independence of signals for SNPs in the gene and bronchodilator response.
全基因组关联研究（GWAS）在识别许多常见疾病和性状的基因座方面发挥着关键作用。在过去十年中，GWAS的数量迅速增加。随着更多GWAS的开展，尚不清楚与感兴趣的性状相关的新信号是否独立于先前与感兴趣的性状相关的同一区域中的单核苷酸多态性（SNP）。确定新关联是否独立于先前信号的一般方法是在先前鉴定的SNP的条件下检查新SNP与感兴趣性状的关联和/或计算两个SNP之间的连锁不平衡（LD）。然而，上位性和SNP与SNP相互作用的作用很少被考虑。通过模拟研究，我们研究了SNP与SNP相互作用在确定两个遗传关联信号独立性时的作用。我们在Github上创建了一个名为gxgRC的R包，以根据用户输入生成这些模拟研究。在哮喘的遗传关联研究中，我们在确定基因和支气管扩张剂反应中SNP信号的独立性时考虑了SNP与SNP相互作用的作用。
