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Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism
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Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism
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Journal Article
Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism
2017
Overview
1,5-anhydroglucitol (1,5-AG) is a biomarker of hyperglycemic excursions associated with diabetic complications. Because of its structural similarity to glucose, genetic studies of 1,5-AG can deliver complementary insights into glucose metabolism. We conducted genome-wide association studies of serum 1,5-AG concentrations in 7,550 European ancestry (EA) and 2,030 African American participants (AA) free of diagnosed diabetes from the ARIC Study. Seven loci in/near
EFNA1
/
SLC50A1
,
MCM6
/
LCT
,
SI
,
MGAM
,
MGAM2
,
SLC5A10
, and
SLC5A1
showed genome-wide significant associations (
P
< 5 × 10
−8
) among EA participants, five of which were novel. Six of the seven loci were successfully replicated in 8,790 independent EA individuals, and
MCM6
/
LCT
and
SLC5A10
were also associated among AA. Most of 1,5-AG-associated index SNPs were not associated with the clinical glycemic markers fasting glucose or the HbA1c, and vice versa. Only the index variant in
SLC5A1
showed a significant association with fasting glucose in the expected opposing direction. Products of genes in all 1,5-AG-associated loci have known roles in carbohydrate digestion and enteral or renal glucose transport, suggesting that genetic variants associated with 1,5-AG influence its concentration via effects on glucose metabolism and handling.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 692/4017
/ Aged
/ Black or African American - genetics
/ Diabetes Mellitus, Type 2 - genetics
/ Diabetes Mellitus, Type 2 - metabolism
/ Diabetes Mellitus, Type 2 - pathology
/ Female
/ Genetic Predisposition to Disease
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomes
/ Glucose
/ Glycated Hemoglobin - genetics
/ Humanities and Social Sciences
/ Humans
/ Kidneys
/ Male
/ Minichromosome Maintenance Complex Component 6 - genetics
/ Science
/ Single-nucleotide polymorphism
