Genome-wide association studies of common diseases often identify a number of disease-related SNPs that reach highly significant p values but at the same time show very low disease odds ratios (ORs), most <1.5 and many <1.2. Despite their statistical significance, associations involving very low ORs explain little about the genetic contribution to the disease and nothing about disease inheritance. A commonly accepted explanation for very low ORs involves a model of polygenic inheritance, i.e., where the disease being studied is caused by a large number of interacting genes, each gene contributing only a small increment to disease risk. Here we demonstrate the perhaps counterintuitive result that, within a reasonable range of disease population prevalences (≤10%), a pure polygenic model is incompatible with very low ORs, unless very large numbers (hundreds or even thousands) of polygenic loci are involved.

中文翻译：

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我们如何解释GWAS中极低的赔率？I.多基因模型。

常见疾病的全基因组关联研究通常会鉴定出许多与疾病相关的SNP，这些SNP达到非常显着的p值，但同时却显示出非常低的疾病几率（OR），大多数<1.5，许多<1.2。尽管它们具有统计学意义，但涉及极低OR的关联对该疾病的遗传贡献几乎没有解释，而对疾病遗传也没有任何解释。普遍接受的关于极低OR的解释涉及一种多基因遗传模型，即所研究的疾病是由大量相互作用的基因引起的，每个基因对疾病风险的贡献很小。在这里，我们证明了可能与直觉相反的结果，即在合理的疾病人群患病率范围（≤10％）内，纯多基因模型与极低的OR不相容，