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New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
- Source :
- Nature Genetics, Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, A U, Wheeler, E, Glazer, N L, Bouatia-Naji, N, Gloyn, A L, Lindgren, C M, Mägi, R, Morris, A P, Randall, J, Johnson, T, Hottenga, J J, de Geus, E J C, Kaprio, J, Kyvik, K O, Pedersen, N L, Perola, M, Posthuma, D, Rivadeneira, F, Uitterlinden, A G, Willems van Dijk, K, van Hoek, M, Vogelzangs, N, Willemsen, G, Witteman, J C M, Zillikens, M C, Penninx, B W J H, Boomsma, D I, van Duijn, C M, Aulchenko, Y S, Waterworth, D, Vollenweider, P, Peltonen, L, Mooser, V, Abecasis, G R, Wareham, N J, Sladek, R, Froguel, P, Watanabe, R M, Meigs, J B, Groop, L C, Boehnke, M, McCarthy, M I, Florez, J C & Barroso, I 2010, ' New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk ', Nature Genetics, vol. 42, no. 2, pp. 105-116 . https://doi.org/10.1038/ng.520, Nature genetics, U32, Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, A U, Wheeler, E, Glazer, N L, Bouatia-Naji, N, Gloyn, A L, Lindgren, C M, Mägi, R, Morris, A P, Randall, J, Johnson, T, Elliott, P, Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P, Grallert, H, Dehghan, A, Hottenga, J J, Franklin, C S, Navarro, P, Song, K, Goel, A, Perry, J R B, Egan, J M, Lajunen, T, Grarup, N, Sparsø, T, Doney, A, Voight, B F, Stringham, H M, Li, M, Kanoni, S, Shrader, P, Cavalcanti-Proença, C, Kumari, M, Qi, L, Timpson, N J, Hayward, C, Vitart, V, Wild, S H, Morris, A, Rudan, I, Wright, A F & Campbell, H & Wilson, J F 2010, ' New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk ', Nature Genetics, vol. 42, no. 2, pp. 105-116 . https://doi.org/10.1038/ng.520, Nature Genetics, 42(2), 105-116. Nature Publishing Group, Yarnell, J 2010, ' New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk ' Nature Genetics, vol. 42, no. 2, pp. 105-119 . DOI: 10.1038/ng.520, Nature Genetics; Vol 42, Nature Genetics, 42(2), 105-U32. Nature Publishing Group, Nature genetics, vol. 42, no. 2, pp. 105-116, Nature Genetics, 42(5), 464-464, Nature Genetics, 42(2), 105, Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, A U, Wheeler, E, Glazer, N L, Bouatia-Naji, N, Gloyn, A L, Lindgren, C M, Mägi, R, Morris, A P, Randall, J, Johnson, T, Elliott, P, Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P, Grallert, H, Dehghan, A, Hottenga, J J, Franklin, C S, Navarro, P, Song, K, Goel, A, Perry, J R B, Egan, J M, Lajunen, T, Grarup, N, Sparsø, T H, Doney, A, Voight, B F, Stringham, H M, Li, M, Kanoni, S, Shrader, P, Cavalcanti-Proença, C, Kumari, M, Lu, Q, Timpson, N J, Gieger, C, Zabena, C, Rocheleau, G, Ingelsson, E, An, P, O'Connell, J, Borch-Johnsen, K, Kyvik, K O & DIAGRAM Consortium 2010, ' New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk ', Nature Genetics, vol. 42, no. 2, pp. 105-16 . https://doi.org/10.1038/ng.520
- Publication Year :
- 2010
-
Abstract
- Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46, 186 nondiabetic participants. Follow-up of 25 loci in up to 76, 558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
- Subjects :
- Blood Glucose
Netherlands Twin Register (NTR)
Candidate gene
Genome-wide association study
Type 2 diabetes
CIRCADIAN CLOCK
TRIGLYCERIDE LEVELS
0302 clinical medicine
Delta-5 Fatty Acid Desaturase
Databases, Genetic
Homeostasis
GENETICS & HEREDITY
Anders Hamsten on behalf of Procardis Consortium
Child
Genetics
PLASMA-GLUCOSE
0303 health sciences
Glucokinase regulatory protein
COMMON VARIANTS
11 Medical And Health Sciences
Fasting
MAGIC investigators
3. Good health
MODEL ASSESSMENT
Life Sciences & Biomedicine
Adult
medicine.medical_specialty
ESSENTIAL COMPONENTS
Adolescent
DNA Copy Number Variations
Alleles
Blood Glucose/genetics
Blood Glucose/metabolism
DNA Copy Number Variations/genetics
Diabetes Mellitus, Type 2/genetics
Fasting/blood
Gene Expression Regulation
Genetic Loci/genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Homeostasis/genetics
Humans
Meta-Analysis as Topic
Polymorphism, Single Nucleotide/genetics
Quantitative Trait Loci/genetics
Quantitative Trait, Heritable
Reproducibility of Results
Quantitative Trait Loci
030209 endocrinology & metabolism
Biology
DIAGRAM Consortium
INSULIN-SECRETION
Polymorphism, Single Nucleotide
Article
Fasting glucose
03 medical and health sciences
Insulin resistance
SDG 3 - Good Health and Well-being
Diabetes mellitus
Internal medicine
genome wide association study
glucose
diabetes type 2
medicine
GIANT Consortium
Allele
GENOME-WIDE ASSOCIATION
Global BPgen Consortium
030304 developmental biology
Glycemic
Science & Technology
genome-wide association beta-cell dysfunction plasma-glucose insulin-secretion triglyceride levels essential components model assessment common variants circadian clock disease risk
DISEASE RISK
06 Biological Sciences
medicine.disease
Endocrinology
Diabetes Mellitus, Type 2
Genetic Loci
biology.protein
BETA-CELL DYSFUNCTION
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 15461718 and 10614036
- Volume :
- 42
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Nature Genetics
- Accession number :
- edsair.doi.dedup.....c31914cd113c85ee43e2a501595f313a
- Full Text :
- https://doi.org/10.1038/ng.520