METHODS: To begin to address this complexity, we attempted to identify genetic interactions between rs16969968, the most replicated SNP associated with smoking quantity, and all SNPs and genes across the genome.
RESULTS: Using the UK Biobank European subsample, we found one SNP, rs1892967, and two genes, PCNA and TMEM230, that showed a significant genome-wide interaction with rs16969968 for log10 CPD and raw CPD, respectively, in a sample of 116 442 individuals who self-reported currently or previously smoking. We extended these analyses to individuals of South Asian descent and meta-analyzed the combined sample of 117 212 individuals of European and South Asian ancestry. We replicated the gene findings in a meta-analysis of five Finnish samples (N=40 140): FinHealth, FINRISK, Finnish Twin Cohort, GeneRISK, and Health-2000-2011.
CONCLUSIONS: To our knowledge, this represents the first reliable epistatic association between single nucleotide polymorphisms for smoking behaviors and provides a novel direction for possible future functional studies related to this interaction. Furthermore, this work demonstrates the feasibility of these analyses by pooling multiple datasets across various ancestries, which may be applied to other top SNPs for smoking and/or other phenotypes.
方法:要开始解决这种复杂性,我们试图确定rs16969968之间的遗传相互作用,rs16969968是与吸烟量相关的复制最多的SNP,以及整个基因组中的所有SNP和基因。
结果:使用英国生物库欧洲子样本,我们发现了一个SNP,rs1892967和两个基因,PCNA和TMEM230,显示出与log10CPD和原始CPD的rs16969968的显著全基因组相互作用,分别,在116442名自我报告目前或以前吸烟的人的样本中。我们将这些分析扩展到南亚血统的个体,并对117212个欧洲和南亚血统的个体的合并样本进行了荟萃分析。我们在对五个芬兰样本(N=40140)的荟萃分析中复制了基因发现:FinHealth,FINRISK,芬兰双队列,GeneRISK,和健康-2000-2011。
结论:据我们所知,这代表了单核苷酸多态性与吸烟行为之间的首次可靠的认知关联,并为未来可能的与这种相互作用相关的功能研究提供了新的方向。此外,这项工作通过汇集不同祖先的多个数据集,证明了这些分析的可行性,它可以应用于吸烟和/或其他表型的其他顶级SNP。