Morris Andrew P
Department of Biostatistics, University of Liverpool, Duncan Building, Daulby Street, Liverpool, L69 3GA, UK,
Curr Diab Rep. 2014;14(11):549. doi: 10.1007/s11892-014-0549-2.
Genome-wide association studies of type 2 diabetes have been extremely successful in discovering loci that contribute genetic effects to susceptibility to the disease. However, at the vast majority of these loci, the variants and transcripts through which these effects on type 2 diabetes are mediated are unknown, limiting progress in defining the pathophysiological basis of the disease. In this review, we will describe available approaches for assaying genetic variation across loci and discuss statistical methods to determine the most likely causal variants in the region. We will consider the utility of trans-ethnic meta-analysis for fine mapping by leveraging the differences in the structure of linkage disequilibrium between diverse populations. Finally, we will discuss progress in fine-mapping type 2 diabetes susceptibility loci to date and consider the prospects for future efforts to localise causal variants for the disease.
2型糖尿病的全基因组关联研究在发现对该疾病易感性有遗传影响的基因座方面极为成功。然而,在绝大多数这些基因座中,介导对2型糖尿病产生这些影响的变异体和转录本尚不清楚,这限制了在确定该疾病病理生理基础方面的进展。在本综述中,我们将描述用于检测基因座间遗传变异的现有方法,并讨论确定该区域最可能的因果变异体的统计方法。我们将考虑跨种族荟萃分析通过利用不同人群之间连锁不平衡结构差异进行精细定位的效用。最后,我们将讨论迄今为止在2型糖尿病易感基因座精细定位方面的进展,并考虑未来定位该疾病因果变异体的努力前景。