Weiss Scott T, Raby Benjamin A, Rogers Angela
Harvard Medical School, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA.
Curr Opin Genet Dev. 2009 Jun;19(3):279-82. doi: 10.1016/j.gde.2009.05.001. Epub 2009 May 28.
Asthma Genetic Association studies have been plagued by methodologic problems that are common in all studies of complex traits: small sample size, lack of replication, and lack of control of population stratification. Despite this, the field has identified 43 replicated genes from association studies. The most frequently replicated are: TNF alpha, IL4, FCERB, Adam 33, and GSTP1. Several genes have been identified by linkage and fine mapping (ADAM33, DPP10, GPR154, and PHF11) and one gene has been identified by GWAS (ORMD3). The major issue is that these genes have been looked at one at a time rather than in some more holistic manner where epistasis is considered. For asthma genetics to begin to have an impact on clinical medicine we need to consider epistatic interaction.
样本量小、缺乏重复性以及缺乏对群体分层的控制。尽管如此,该领域已从关联研究中鉴定出43个重复基因。最常被重复鉴定的基因有:肿瘤坏死因子α、白细胞介素4、高亲和力IgE受体β链、解聚素金属蛋白酶33和谷胱甘肽S-转移酶P1。通过连锁分析和精细定位鉴定出了几个基因(解聚素金属蛋白酶33、二肽基肽酶10、G蛋白偶联受体154和含PHD结构域蛋白11),通过全基因组关联研究鉴定出了一个基因(成骨相关膜蛋白3)。主要问题在于,这些基因是逐个进行研究的,而不是以某种更全面的方式,即考虑上位性的方式进行研究。为了使哮喘遗传学开始对临床医学产生影响,我们需要考虑上位性相互作用。