FTO、IRX3／5，孰是孰非？

Which is the culprit in obesity, FTO or IRX3/5？

多项针对肥胖症的大规模全基因组关联研究（GWAS）结果表明，位于FTO基因1号内含子的多个多态性位点与肥胖发生风险密切相关，不仅是所有GWAS关联位点中统计学差异最为明显的，且是效应最强的一簇；后续临床、动物模型或分子生物学研究也支持Fro在肥胖发生中的重要作用。然而，《The New England Journal of Medicine》杂志刚刚公布的一项研究表明，这些关联位点的真正效应基因是IRX3／5，这2个基因表达水平改变才是导致该风险位点被反复证明与肥胖相关的原因。我们该如何看待这一肥胖遗传学研究中最引人注目的事件？究竟谁是普通型肥胖症的元凶？这些问题尚待探究。

A dozens of variants in intron 1 of FTO gene have been found to be significantly associated with obesity by a serious genome-wide association studies （GWAS） in past eight years. Very recently, The New England Journal of Medicine published an important genetic study of obesity, which challenged the point of FTO causing obesity directly. The researchers find one of the variants changes the binding ability of upstream regulator to IRX3/IRX5 and thus promotes IRX3/IRX5 expression instead of FTO. Which one is the real causal gene of common obesity, FTO, IRX3/5, both, or neither？ All these questions need to be answered.