We assembled an ancestrally diverse collection of genome-wide association studies of type 2 diabetes (T2D) in 180,834 cases and 1,159,055 controls (48.9% non-European descent). We identified 277 loci at genome-wide significance (p<5x10-8), including 237 attaining a more stringent trans-ancestry threshold (p<5x10-9), which were delineated to 338 distinct association signals. Trans-ancestry meta-regression offered substantial enhancements to fine-mapping, with 58.6% of associations more precisely localised due to population diversity, and 54.4% of signals resolved to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying foundations for functional investigations. Trans-ancestry genetic risk scores enhanced transferability across diverse populations, providing a step towards more effective clinical translation to improve global health.

中文翻译：

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2类糖尿病的跨祖先遗传研究突出了不同人群发现和翻译的能力

我们收集了180,834例病例和1,159,055例对照（48.9％的非欧洲血统）的祖先多样化的2型糖尿病（T2D）全基因组关联研究集合。我们在全基因组意义上鉴定了277个基因座（p <5x10-8），包括237个达到更严格的先祖阈值（p <5x10-9），这些基因座被描述为338个不同的关联信号。跨祖先的元回归极大地增强了精细映射，由于人口多样性，58.6％的关联更精确地定位，54.4％的信号解析为单个变异的后验概率> 50％。这种改进的精细映射可以系统评估候选病因基因和介导T2D关联的分子机制，从而为功能研究奠定基础。