Skip to main content
Download PDF
- Main
Multi-ethnic GWAS and fine-mapping of glycaemic traits identify novel loci in the PAGE Study
- Downie, Carolina G;
- Dimos, Sofia F;
- Bien, Stephanie A;
- Hu, Yao;
- Darst, Burcu F;
- Polfus, Linda M;
- Wang, Yujie;
- Wojcik, Genevieve L;
- Tao, Ran;
- Raffield, Laura M;
- Armstrong, Nicole D;
- Polikowsky, Hannah G;
- Below, Jennifer E;
- Correa, Adolfo;
- Irvin, Marguerite R;
- Rasmussen-Torvik, Laura JF;
- Carlson, Christopher S;
- Phillips, Lawrence S;
- Liu, Simin;
- Pankow, James S;
- Rich, Stephen S;
- Rotter, Jerome I;
- Buyske, Steven;
- Matise, Tara C;
- North, Kari E;
- Avery, Christy L;
- Haiman, Christopher A;
- Loos, Ruth JF;
- Kooperberg, Charles;
- Graff, Mariaelisa;
- Highland, Heather M
Published Web Location
https://doi.org/10.1007/s00125-021-05635-9Abstract
Aims/hypothesis
Type 2 diabetes is a growing global public health challenge. Investigating quantitative traits, including fasting glucose, fasting insulin and HbA1c, that serve as early markers of type 2 diabetes progression may lead to a deeper understanding of the genetic aetiology of type 2 diabetes development. Previous genome-wide association studies (GWAS) have identified over 500 loci associated with type 2 diabetes, glycaemic traits and insulin-related traits. However, most of these findings were based only on populations of European ancestry. To address this research gap, we examined the genetic basis of fasting glucose, fasting insulin and HbA1c in participants of the diverse Population Architecture using Genomics and Epidemiology (PAGE) Study.Methods
We conducted a GWAS of fasting glucose (n = 52,267), fasting insulin (n = 48,395) and HbA1c (n = 23,357) in participants without diabetes from the diverse PAGE Study (23% self-reported African American, 46% Hispanic/Latino, 40% European, 4% Asian, 3% Native Hawaiian, 0.8% Native American), performing transethnic and population-specific GWAS meta-analyses, followed by fine-mapping to identify and characterise novel loci and independent secondary signals in known loci.Results
Four novel associations were identified (p < 5 × 10-9), including three loci associated with fasting insulin, and a novel, low-frequency African American-specific locus associated with fasting glucose. Additionally, seven secondary signals were identified, including novel independent secondary signals for fasting glucose at the known GCK locus and for fasting insulin at the known PPP1R3B locus in transethnic meta-analysis.Conclusions/interpretation
Our findings provide new insights into the genetic architecture of glycaemic traits and highlight the continued importance of conducting genetic studies in diverse populations.Data availability
Full summary statistics from each of the population-specific and transethnic results are available at NHGRI-EBI GWAS catalog ( https://www.ebi.ac.uk/gwas/downloads/summary-statistics ).Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
Main Content
For improved accessibility of PDF content, download the file to your device.
Enter the password to open this PDF file:
File name:
-
File size:
-
Title:
-
Author:
-
Subject:
-
Keywords:
-
Creation Date:
-
Modification Date:
-
Creator:
-
PDF Producer:
-
PDF Version:
-
Page Count:
-
Page Size:
-
Fast Web View:
-
Preparing document for printing…
0%