背景回顾：Genome-wide association studies (GWAS) have become a standard approach for exploring the genetic basis of phenotypic variation. 

提出问题：However, correlation is not causation, and only a tiny fraction of all associations have been experimentally confirmed.

提出假设：One practical problem is that a peak of association does not always pinpoint a causal gene, but may instead be tagging multiple causal variants.

主要研究：In this study, we reanalyze a previously reported peak associated with flowering time traits in Swedish Arabidopsis thaliana population. 

先前结果：The peak appeared to pinpoint the AOP2/AOP3 cluster of glucosinolate biosynthesis genes, which is known to be responsible for natural variation in herbivore resistance. 

新假设：Here we propose an alternative hypothesis, by demonstrating that the AOP2/AOP3 flowering association can be wholly accounted for by allelic variation in two flanking genes with clear roles in regulating flowering: NDX1, a regulator of the main flowering time controller FLC, and GA1, which plays a central role in gibberellin synthesis and is required for flowering under some conditions.

结论：In other words, we propose that the AOP2/AOP3 flowering-time association may be yet another example of a spurious, “synthetic” association, arising from trying to fit a single-locus model in the presence of two statistically associated causative loci. 

总结：We conclude that caution is needed when using GWAS for fine-mapping.

 摘 要 

全基因组关联研究（GWAS）已成为研究表型变异遗传基础的标准方法。然而，相关性并不是因果关系，所有的关联中只有很小一部分已经被实验证实。一个实际问题是，关联的峰值并不总是指向一个因果基因，而是可能标记了多个因果关系基因的变异体。在该项研究中，作者重新分析了瑞典科学家先前报道的拟南芥群体开花性状的GWAS图中出现的高点峰值。这个峰值看起来像是定位到了硫代葡萄糖苷的生物合成基因（AOP2/AOP3）基因簇，这是已知的饲草对草食动物啃食行为的抗性天然变异。该文作者提出了另一种假设。通过分析证明这种AOP2/AOP3与植株开花关联的机制，完全可以由两个在调控开花中有明确作用的侧翼基因的等位变异来解释：一个是NDX1基因，该基因是开花时间控制基因FLC的主要调控因子；另一个是在赤霉素的合成中起核心作用的GA1基因，是特定的条件下开花所必需的。换句话说，作者认为AOP2/AOP3开花时间关联可能是另一种虚假的“合成”关联的例子（即人为的牵强附会），这是由于在实际上存在两个统计相关的“有因位点”（two statistically associated causative loci），但是作者仍然试图将之拟合成“单位点模型”（a single-locus model）而造成的谬误。因此作者认为，在使用GWAS进行精细作图时，对于结果的应用需要十分谨慎。