Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism

Man Li, Nisa Maruthur, Stephanie J. Loomis, Maik Pietzner, Kari E. North, Hao Mei, Alanna C. Morrison, Nele Friedrich, James S. Pankow, Matthias Nauck, Eric Boerwinkle, Alexander Teumer, Elizabeth Selvin, Anna Köttgen

Research output: Contribution to journalArticle

Abstract

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 theHbA1c, 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.

Original languageEnglish (US)
Article number2812
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Genetic Loci
Genome-Wide Association Study
Glucose
African Americans
Fasting
Biomarkers
Diabetes Complications
Small Intestine
Single Nucleotide Polymorphism
1,5-anhydroglucitol
Digestion
Carbohydrates
Genome
Kidney
Serum
Genes

ASJC Scopus subject areas

  • General

Cite this

Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism. / Li, Man; Maruthur, Nisa; Loomis, Stephanie J.; Pietzner, Maik; North, Kari E.; Mei, Hao; Morrison, Alanna C.; Friedrich, Nele; Pankow, James S.; Nauck, Matthias; Boerwinkle, Eric; Teumer, Alexander; Selvin, Elizabeth; Köttgen, Anna.

In: Scientific Reports, Vol. 7, No. 1, 2812, 01.12.2017.

Research output: Contribution to journalArticle

Li, M, Maruthur, N, Loomis, SJ, Pietzner, M, North, KE, Mei, H, Morrison, AC, Friedrich, N, Pankow, JS, Nauck, M, Boerwinkle, E, Teumer, A, Selvin, E & Köttgen, A 2017, 'Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism', Scientific Reports, vol. 7, no. 1, 2812. https://doi.org/10.1038/s41598-017-02287-x
Li, Man ; Maruthur, Nisa ; Loomis, Stephanie J. ; Pietzner, Maik ; North, Kari E. ; Mei, Hao ; Morrison, Alanna C. ; Friedrich, Nele ; Pankow, James S. ; Nauck, Matthias ; Boerwinkle, Eric ; Teumer, Alexander ; Selvin, Elizabeth ; Köttgen, Anna. / Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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