Integrative Study of Genomics, Transcriptomics and Metabolomics in Type 2 Diabetes

 描述(申请人提供)：2型糖尿病(T2D)在美国非常流行，少数族裔人群的患病率(9-15.9%)高于非西班牙裔白人(7.6%)。利用全基因组关联研究和下一代测序方法的大型多血统联盟的努力已经成功地识别了大量与T2D相关的常见和低频遗传变异。然而，大多数疾病的遗传性仍然无法解释， 各自的因果变量是有限的。该项目的目的是使用多个祖先的GWAMeta分析，辅以新的分析方法，以及对特征良好的样品进行物候学研究，以实现以下具体目标。目的1：发现和精细定位T2D基因座，并将其归因于用于跨祖先GWAMeta分析的祖先特异性参考品。目的：以基因-基因和基因-环境互作为靶点，寻找新的T2D基因座，用于跨系遗传荟萃分析。目的3：使用临床代谢学、基因组学、转录组学和代谢组学对综合表征数据集的“表型组学”进行综合分析，以确定与T2D相关的变异和基因座的功能特征。

 DESCRIPTION (provided by applicant): Type 2 diabetes (T2D) is highly prevalent in the US with higher prevalence in the minority populations (9-15.9%) as compared to non-Hispanic whites (7.6%). Efforts from large multi- ancestry consortia using genome-wide association studies (GWAS) and next generation sequencing approaches have successfully identified a large number of common and low frequency genetic variants associated with T2D. However, the majority of disease heritability remains unexplained and identification and characterization of the respective causal variants is limited. This project aims to use multi-ancestry GWAS meta-analysis complemented with novel analytical approach, as well as phenomic studies in well-characterized samples to achieve the following specific aims. Aim 1: Discovery and fine mapping of T2D loci using GWAS imputed to ancestry-specific reference panels for trans-ancestry GWAS meta-analysis. Aim 2: Targeted gene-gene and gene-environment interaction to identify novel T2D loci for trans-ancestry GWAS meta-analysis. Aim 3: Integrative "Phenomics" analyses of comprehensively characterized datasets using clinical metabolic, genomics, transcriptomics, and metabolomics for functional characterization of variants and loci associated with T2D.