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

 描述（由申请人提供）：2型糖尿病（T2 D）在美国非常普遍，与非西班牙裔白人（7.6%）相比，少数民族人群（9-15.9%）的患病率更高。来自大型多祖先联盟的使用全基因组关联研究（GWAS）和下一代测序方法的努力已经成功地鉴定了大量与T2 D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。该项目旨在使用多祖先GWAS荟萃分析，辅以新的分析方法，以及在表征良好的样本中进行表型研究，以实现以下特定目标。目的1：使用GWAS发现和精细定位T2 D基因座，将其输入到祖先特异性参考组，用于跨祖先GWAS荟萃分析。目的2：靶向基因-基因和基因-环境相互作用，以确定新的T2 D基因座用于跨祖先GWAS荟萃分析。目标3：使用临床代谢、基因组学、转录组学和代谢组学对全面表征的数据集进行综合“表型组学”分析，用于与T2 D相关的变体和基因座的功能表征。

 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.