New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

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New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. / Dupuis, Josée; Langenberg, Claudia; Prokopenko, Inga; Saxena, Richa; Soranzo, Nicole; Jackson, Anne U; Wheeler, Eleanor; Glazer, Nicole L; Bouatia-Naji, Nabila; Gloyn, Anna L; Lindgren, Cecilia M; Mägi, Reedik; Morris, Andrew P; Randall, Joshua; Johnson, Toby; Elliott, Paul; Rybin, Denis; Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Henneman, Peter; Grallert, Harald; Dehghan, Abbas; Hottenga, Jouke Jan; Franklin, Christopher S; Navarro, Pau; Song, Kijoung; Goel, Anuj; Perry, John R B; Egan, Josephine M; Lajunen, Taina; Grarup, Niels; Sparsø, Thomas; Doney, Alex; Voight, Benjamin F; Stringham, Heather M; Li, Man; Kanoni, Stavroula; Shrader, Peter; Cavalcanti-Proença, Christine; Kumari, Meena; Qi, Lu; Timpson, Nicholas J; Gieger, Christian; Zabena, Carina; Rocheleau, Ghislain; Ingelsson, Erik; An, Ping; Jørgensen, Torben; Hansen, Torben; Pedersen, Oluf; DIAGRAM Consortium.

In: Nature Genetics, Vol. 42, No. 2, 01.02.2010, p. 105-16.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, AU, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Gloyn, AL, Lindgren, CM, Mägi, R, Morris, AP, Randall, J, Johnson, T, Elliott, P, Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P, Grallert, H, Dehghan, A, Hottenga, JJ, Franklin, CS, Navarro, P, Song, K, Goel, A, Perry, JRB, Egan, JM, Lajunen, T, Grarup, N, Sparsø, T, Doney, A, Voight, BF, Stringham, HM, Li, M, Kanoni, S, Shrader, P, Cavalcanti-Proença, C, Kumari, M, Qi, L, Timpson, NJ, Gieger, C, Zabena, C, Rocheleau, G, Ingelsson, E, An, P, Jørgensen, T, Hansen, T, Pedersen, 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

APA

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., ... DIAGRAM Consortium (2010). New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nature Genetics, 42(2), 105-16. https://doi.org/10.1038/ng.520

Vancouver

Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nature Genetics. 2010 Feb 1;42(2):105-16. https://doi.org/10.1038/ng.520

Author

Dupuis, Josée ; Langenberg, Claudia ; Prokopenko, Inga ; Saxena, Richa ; Soranzo, Nicole ; Jackson, Anne U ; Wheeler, Eleanor ; Glazer, Nicole L ; Bouatia-Naji, Nabila ; Gloyn, Anna L ; Lindgren, Cecilia M ; Mägi, Reedik ; Morris, Andrew P ; Randall, Joshua ; Johnson, Toby ; Elliott, Paul ; Rybin, Denis ; Thorleifsson, Gudmar ; Steinthorsdottir, Valgerdur ; Henneman, Peter ; Grallert, Harald ; Dehghan, Abbas ; Hottenga, Jouke Jan ; Franklin, Christopher S ; Navarro, Pau ; Song, Kijoung ; Goel, Anuj ; Perry, John R B ; Egan, Josephine M ; Lajunen, Taina ; Grarup, Niels ; Sparsø, Thomas ; Doney, Alex ; Voight, Benjamin F ; Stringham, Heather M ; Li, Man ; Kanoni, Stavroula ; Shrader, Peter ; Cavalcanti-Proença, Christine ; Kumari, Meena ; Qi, Lu ; Timpson, Nicholas J ; Gieger, Christian ; Zabena, Carina ; Rocheleau, Ghislain ; Ingelsson, Erik ; An, Ping ; Jørgensen, Torben ; Hansen, Torben ; Pedersen, Oluf ; DIAGRAM Consortium. / New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. In: Nature Genetics. 2010 ; Vol. 42, No. 2. pp. 105-16.

Bibtex

@article{bc61ce740eb84056b7a0f2a9384f8ee4,
title = "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk",
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.",
keywords = "Adolescent, Adult, Alleles, Blood Glucose, Child, DNA Copy Number Variations, Databases, Genetic, Diabetes Mellitus, Type 2, Fasting, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Homeostasis, Humans, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Reproducibility of Results",
author = "Jos{\'e}e Dupuis and Claudia Langenberg and Inga Prokopenko and Richa Saxena and Nicole Soranzo and Jackson, {Anne U} and Eleanor Wheeler and Glazer, {Nicole L} and Nabila Bouatia-Naji and Gloyn, {Anna L} and Lindgren, {Cecilia M} and Reedik M{\"a}gi and Morris, {Andrew P} and Joshua Randall and Toby Johnson and Paul Elliott and Denis Rybin and Gudmar Thorleifsson and Valgerdur Steinthorsdottir and Peter Henneman and Harald Grallert and Abbas Dehghan and Hottenga, {Jouke Jan} and Franklin, {Christopher S} and Pau Navarro and Kijoung Song and Anuj Goel and Perry, {John R B} and Egan, {Josephine M} and Taina Lajunen and Niels Grarup and Thomas Spars{\o} and Alex Doney and Voight, {Benjamin F} and Stringham, {Heather M} and Man Li and Stavroula Kanoni and Peter Shrader and Christine Cavalcanti-Proen{\c c}a and Meena Kumari and Lu Qi and Timpson, {Nicholas J} and Christian Gieger and Carina Zabena and Ghislain Rocheleau and Erik Ingelsson and Ping An and Torben J{\o}rgensen and Torben Hansen and Oluf Pedersen and {DIAGRAM Consortium}",
year = "2010",
month = feb,
day = "1",
doi = "10.1038/ng.520",
language = "English",
volume = "42",
pages = "105--16",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "2",

}

RIS

TY - JOUR

T1 - New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

AU - Dupuis, Josée

AU - Langenberg, Claudia

AU - Prokopenko, Inga

AU - Saxena, Richa

AU - Soranzo, Nicole

AU - Jackson, Anne U

AU - Wheeler, Eleanor

AU - Glazer, Nicole L

AU - Bouatia-Naji, Nabila

AU - Gloyn, Anna L

AU - Lindgren, Cecilia M

AU - Mägi, Reedik

AU - Morris, Andrew P

AU - Randall, Joshua

AU - Johnson, Toby

AU - Elliott, Paul

AU - Rybin, Denis

AU - Thorleifsson, Gudmar

AU - Steinthorsdottir, Valgerdur

AU - Henneman, Peter

AU - Grallert, Harald

AU - Dehghan, Abbas

AU - Hottenga, Jouke Jan

AU - Franklin, Christopher S

AU - Navarro, Pau

AU - Song, Kijoung

AU - Goel, Anuj

AU - Perry, John R B

AU - Egan, Josephine M

AU - Lajunen, Taina

AU - Grarup, Niels

AU - Sparsø, Thomas

AU - Doney, Alex

AU - Voight, Benjamin F

AU - Stringham, Heather M

AU - Li, Man

AU - Kanoni, Stavroula

AU - Shrader, Peter

AU - Cavalcanti-Proença, Christine

AU - Kumari, Meena

AU - Qi, Lu

AU - Timpson, Nicholas J

AU - Gieger, Christian

AU - Zabena, Carina

AU - Rocheleau, Ghislain

AU - Ingelsson, Erik

AU - An, Ping

AU - Jørgensen, Torben

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - DIAGRAM Consortium

PY - 2010/2/1

Y1 - 2010/2/1

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Alleles

KW - Blood Glucose

KW - Child

KW - DNA Copy Number Variations

KW - Databases, Genetic

KW - Diabetes Mellitus, Type 2

KW - Fasting

KW - Gene Expression Regulation

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Homeostasis

KW - Humans

KW - Meta-Analysis as Topic

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

KW - Quantitative Trait, Heritable

KW - Reproducibility of Results

U2 - 10.1038/ng.520

DO - 10.1038/ng.520

M3 - Journal article

C2 - 20081858

VL - 42

SP - 105

EP - 116

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 2

ER -

ID: 33503026