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

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...

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Autores principales:	Man Li, Nisa M. 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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1df2dff7ba174bee924f36917964fed9
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spelling	oai:doaj.org-article:1df2dff7ba174bee924f36917964fed92021-12-02T11:52:17ZGenome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism10.1038/s41598-017-02287-x2045-2322https://doaj.org/article/1df2dff7ba174bee924f36917964fed92017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02287-xhttps://doaj.org/toc/2045-2322Abstract 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.Man LiNisa M. MaruthurStephanie J. LoomisMaik PietznerKari E. NorthHao MeiAlanna C. MorrisonNele FriedrichJames S. PankowMatthias NauckEric BoerwinkleAlexander TeumerElizabeth SelvinAnna KöttgenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Man Li Nisa M. 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 Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism
description	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 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.
format	article
author	Man Li Nisa M. 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
author_facet	Man Li Nisa M. 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
author_sort	Man Li
title	Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism
title_short	Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism
title_full	Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism
title_fullStr	Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism
title_full_unstemmed	Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism
title_sort	genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1df2dff7ba174bee924f36917964fed9
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Genome-wide association study of 1,5-anhydroglucitol identifies novel genetic loci linked to glucose metabolism

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