Faculty, Staff and Student Publications
Publication Date
9-1-2024
Journal
Diabetes
DOI
10.2337/db23-0318
PMID
38869630
PMCID
PMC11333373
PubMedCentral® Posted Date
6-13-2024
PubMedCentral® Full Text Version
Post-print
Abstract
Genetic studies of nontraditional glycemic biomarkers, glycated albumin and fructosamine, can shed light on unknown aspects of type 2 diabetes genetics and biology. We performed a multiphenotype genome-wide association study of glycated albumin and fructosamine from 7,395 White and 2,016 Black participants in the Atherosclerosis Risk in Communities (ARIC) study on common variants from genotyped/imputed data. We discovered two genome-wide significant loci, one mapping to a known type 2 diabetes gene (ARAP1/STARD10) and another mapping to a novel region (UGT1A complex of genes), using multiomics gene-mapping strategies in diabetes-relevant tissues. We identified additional loci that were ancestry- and sex-specific (e.g., PRKCA in African ancestry, FCGRT in European ancestry, TEX29 in males). Further, we implemented multiphenotype gene-burden tests on whole-exome sequence data from 6,590 White and 2,309 Black ARIC participants. Ten variant sets annotated to genes across different variant aggregation strategies were exome-wide significant only in multiancestry analysis, of which CD1D, EGFL7/AGPAT2, and MIR126 had notable enrichment of rare predicted loss of function variants in African ancestry despite smaller sample sizes. Overall, 8 of 14 discovered loci and genes were implicated to influence these biomarkers via glycemic pathways, and most of them were not previously implicated in studies of type 2 diabetes. This study illustrates improved locus discovery and potential effector gene discovery by leveraging joint patterns of related biomarkers across the entire allele frequency spectrum in multiancestry analysis. Future investigation of the loci and genes potentially acting through glycemic pathways may help us better understand the risk of developing type 2 diabetes.
Keywords
Female, Humans, Male, Middle Aged, Biomarkers, Diabetes Mellitus, Type 2, Fructosamine, Genetic Variation, Genome-Wide Association Study, Glycated Serum Albumin, Multivariate Analysis, Polymorphism, Single Nucleotide, Serum Albumin, White People, Black People
Published Open-Access
yes
Recommended Citation
Ray, Debashree; Loomis, Stephanie J; Venkataraghavan, Sowmya; et al., "Characterizing Common and Rare Variations in Nontraditional Glycemic Biomarkers Using Multivariate Approaches on Multiancestry ARIC Study" (2024). Faculty, Staff and Student Publications. 1366.
https://digitalcommons.library.tmc.edu/uthsph_docs/1366