中文摘要：

近10年来兴起的全基因组关联分析（Genome—wide association study,GWAS）相关研究结果获得了大量与2型糖尿病相关的候选易感基因，了解这些候选基因在正常人群中的遗传多样性程度以及在不同人群间的遗传差异，不但有助于阐明2型糖尿病的遗传机理，而且对于今后在特定人群中进行2型糖尿病发病机制的深入研究具有指导意义。本研究通过对GWAS数据库和相关文献的搜索和整理确定了170个与2型糖尿病相关的基因或基因区域；随后基于千人基因组计划的全基因组测序数据对这些候选基因在世界范围内14个人群间的遗传多样性进行了比较分析；进一步确定了在人群间存在显著差异的易感基因，并分析了这些基因的多样性特征。在所研究的14个世界人群中，2型糖尿病候选易感基因的遗传多样性与基因组范围的平均水平没有显著差异；但其中8个易感基因IL20RA、RNMTL1-NXN、NOTCH2、ADRA2A—BTBD7P2、TBC1D4、RBM38-HMGBIP1、UBE2E2和PPARD在群体间呈现显著差异，其中最明显的是IL20RA基因（FST=0．152），该易感基因在非洲人群和非非洲人群问存在显著等位基因频率和单倍型频率差异。14个人群中易感基因遗传结构差异的主要原因是由于非洲人群与非非洲人群之间的群体遗传结构的不同所造成的。进一步比较东西方人群间的2型糖尿病候选基因遗传结构差异，发现在东西方人群中同样存在明显的群体遗传结构差别，其中DGKB—AGMO（FsT=0．173）和JAZF1（Fs，=0．182）是差异最显著的易感基因。本研究通过对群体间2型糖尿病易感基因遗传结构进行比较，鉴别出一些差异特别显著的易感基因，对今后2型糖尿病易感基因与不同人群间发病率和易感性差异的相关研究提供重要参考。

英文摘要：

Over the last decade, a larger number of type 2 diabetes mellitus （T2DM） susceptible candidate genes have been reported by numerous genome-wide association studies （GWAS）. Understanding the genetic diversity of these candidate genes among worldwide populations not only facilitates to elucidating the genetic mechanism of T2DM, but also provides guidance to further studies ofpathogenesis of T2DM in any certain population. In this study, we identified 170 genes or genomic regions associated with T2DM by searching the GWAS databases and related literatures. We next ana- lyzed the genetic diversity of these genes （or genomic regions） among present-day human populations by curetting the 1000 Genomes Projects phase l dataset covering 14 worldwide populations. We further compared the characteristics of T2DM genes in different populations, No significant differences of genetic diversity were observed among the 14 worldwide pop- ulations between the T2DM candidate genes and the non-T2DM genes in terms of overall pattern. However, we observed some genes, such as IL2ORA, RNMTL1-NXN, NOTCH2, ADRA2A-BTBD7P2, TBC1D4, RBM38-HMGB1P1, UBE2E2, and PPARD, show considerable differentiation between populations. In particular, IL20RA （FDT=0.1521） displays the greatest population difference which is mainly contributed by that between Africans and non-Africans. Moreover, we revealed ge- netic differences between East Asians and Europeans on some candidate genes such as DGKB-AGMO （Fs-r=0.173） and JAZF1 （FsT=0.182）. Our results indicate that some T2DM susceptible candidate genes harbor highly-differentiated va- riants between populations. These analyses, despite preliminary, should advance our understanding of the population dif- ference of susceptibility to T2DM and provide insightful reference that future studies can relay on.