Multi-ethnic GWAS and fine-mapping of glycaemic traits identify novel loci in the PAGE Study – published online 24/12/2021

Carolina G. Downie, Sofia F. Dimos, Stephanie A. Bien, Yao Hu, Burcu F. Darst, Linda M. Polfus, Yujie Wang, Genevieve L. Wojcik, Ran Tao, Laura M. Raffield, Nicole D. Armstrong, Hannah G. Polikowsky, Jennifer E. Below, Adolfo Correa, Marguerite R. Irvin, Laura J. F. Rasmussen-Torvik, Christopher S. Carlson, Lawrence S. Phillips, Simin Liu, James S. Pankow, Stephen S. Rich, Jerome I. Rotter, Steven Buyske, Tara C. Matise, Kari E. North, Christy L. Avery, Christopher A. Haiman, Ruth J. F. Loos, Charles Kooperberg, Mariaelisa Graff, Heather M. Highland

Previous genome-wide association studies (GWAS) have identified over 500 loci associated with type 2 diabetes and glycaemic-related traits. However, most of these studies were conducted in populations of European ancestry. This lack of ancestral diversity hinders efforts to identify novel loci, refine causal signals through fine-mapping, and develop equitable genetic approaches for precision medicine and risk prediction. In this issue, Downie et al (https://doi.org/10.1007/s00125-021-05635-9) identify novel glycaemic trait loci in the ancestrally diverse Population Architecture using Genomics and Epidemiology (PAGE) Study. Specifically, the authors identify three fasting insulin novel loci in a transethnic meta-analysis, one novel low-frequency fasting glucose locus in an African American-specific analysis, and novel independent secondary signals at known fasting glucose and insulin loci. The authors conclude that these findings highlight the continued importance of conducting genetic studies in diverse populations and provide new insights into the genetic architecture of glycaemic traits.

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