Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes

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Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes. / Ahluwalia, Tarun Veer Singh; Allin, Kristine Højgaard; Sandholt, Camilla Helene; Sparsø, Thomas Hempel; Jørgensen, Marit Eika; Rowe, Michael; Christensen, Cramer; Brandslund, Ivan; Lauritzen, Torsten; Linneberg, Allan; Husemoen, Lise-Lotte; Jørgensen, Torben; Hansen, Torben; Grarup, Niels; Pedersen, Oluf.

In: The Journal of clinical endocrinology and metabolism, Vol. 100, No. 4, 04.2015, p. E664-71.

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

Harvard

Ahluwalia, TVS, Allin, KH, Sandholt, CH, Sparsø, TH, Jørgensen, ME, Rowe, M, Christensen, C, Brandslund, I, Lauritzen, T, Linneberg, A, Husemoen, L-L, Jørgensen, T, Hansen, T, Grarup, N & Pedersen, O 2015, 'Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes', The Journal of clinical endocrinology and metabolism, vol. 100, no. 4, pp. E664-71. https://doi.org/10.1210/jc.2014-3677

APA

Ahluwalia, T. V. S., Allin, K. H., Sandholt, C. H., Sparsø, T. H., Jørgensen, M. E., Rowe, M., Christensen, C., Brandslund, I., Lauritzen, T., Linneberg, A., Husemoen, L-L., Jørgensen, T., Hansen, T., Grarup, N., & Pedersen, O. (2015). Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes. The Journal of clinical endocrinology and metabolism, 100(4), E664-71. https://doi.org/10.1210/jc.2014-3677

Vancouver

Ahluwalia TVS, Allin KH, Sandholt CH, Sparsø TH, Jørgensen ME, Rowe M et al. Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes. The Journal of clinical endocrinology and metabolism. 2015 Apr;100(4):E664-71. https://doi.org/10.1210/jc.2014-3677

Author

Ahluwalia, Tarun Veer Singh ; Allin, Kristine Højgaard ; Sandholt, Camilla Helene ; Sparsø, Thomas Hempel ; Jørgensen, Marit Eika ; Rowe, Michael ; Christensen, Cramer ; Brandslund, Ivan ; Lauritzen, Torsten ; Linneberg, Allan ; Husemoen, Lise-Lotte ; Jørgensen, Torben ; Hansen, Torben ; Grarup, Niels ; Pedersen, Oluf. / Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes. In: The Journal of clinical endocrinology and metabolism. 2015 ; Vol. 100, No. 4. pp. E664-71.

Bibtex

@article{9bd4e0c6b3a04b22a4ff46cd2e0cd762,
title = "Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes",
abstract = "CONTEXT: Type 2 diabetes (T2D) prevalence is spiraling globally, and knowledge of its pathophysiological signatures is crucial for a better understanding and treatment of the disease.OBJECTIVE: We aimed to discover underlying coding genetic variants influencing fasting serum levels of nine biomarkers associated with T2D: adiponectin, C-reactive protein, ferritin, heat shock 70-kDa protein 1B, IGF binding protein 1 and IGF binding protein 2, IL-18, IL-2 receptor-α, and leptin.DESIGN AND PARTICIPANTS: A population-based sample of 6215 adult Danes was genotyped for 16 340 coding single-nucleotide polymorphisms and were tested for association with each biomarker. Identified loci were tested for association with T2D through a large-scale meta-analysis involving up to 17 024 T2D cases and up to 64 186 controls.RESULTS: We discovered 11 associations between single-nucleotide polymorphisms and five distinct biomarkers at a study-wide P < 3.4 × 10(-7). Nine associations were novel: IL18: BIRC6, RAD17, MARVELD2; ferritin: F5; IGF binding protein 1: SERPING1, KLKB, GCKR, CELSR2, and heat shock 70-kDa protein 1B: CFH. Three of the identified loci (CELSR2, HNF1A, and GCKR) were significantly associated with T2D, of which the association with the CELSR2 locus has not been shown previously.CONCLUSION: The identified loci influence processes related to insulin signaling, cell communication, immune function, apoptosis, DNA repair, and oxidative stress, all of which could provide a rationale for novel diabetes therapeutic strategies.",
author = "Ahluwalia, {Tarun Veer Singh} and Allin, {Kristine H{\o}jgaard} and Sandholt, {Camilla Helene} and Spars{\o}, {Thomas Hempel} and J{\o}rgensen, {Marit Eika} and Michael Rowe and Cramer Christensen and Ivan Brandslund and Torsten Lauritzen and Allan Linneberg and Lise-Lotte Husemoen and Torben J{\o}rgensen and Torben Hansen and Niels Grarup and Oluf Pedersen",
year = "2015",
month = apr,
doi = "10.1210/jc.2014-3677",
language = "English",
volume = "100",
pages = "E664--71",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "4",

}

RIS

TY - JOUR

T1 - Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes

AU - Ahluwalia, Tarun Veer Singh

AU - Allin, Kristine Højgaard

AU - Sandholt, Camilla Helene

AU - Sparsø, Thomas Hempel

AU - Jørgensen, Marit Eika

AU - Rowe, Michael

AU - Christensen, Cramer

AU - Brandslund, Ivan

AU - Lauritzen, Torsten

AU - Linneberg, Allan

AU - Husemoen, Lise-Lotte

AU - Jørgensen, Torben

AU - Hansen, Torben

AU - Grarup, Niels

AU - Pedersen, Oluf

PY - 2015/4

Y1 - 2015/4

N2 - CONTEXT: Type 2 diabetes (T2D) prevalence is spiraling globally, and knowledge of its pathophysiological signatures is crucial for a better understanding and treatment of the disease.OBJECTIVE: We aimed to discover underlying coding genetic variants influencing fasting serum levels of nine biomarkers associated with T2D: adiponectin, C-reactive protein, ferritin, heat shock 70-kDa protein 1B, IGF binding protein 1 and IGF binding protein 2, IL-18, IL-2 receptor-α, and leptin.DESIGN AND PARTICIPANTS: A population-based sample of 6215 adult Danes was genotyped for 16 340 coding single-nucleotide polymorphisms and were tested for association with each biomarker. Identified loci were tested for association with T2D through a large-scale meta-analysis involving up to 17 024 T2D cases and up to 64 186 controls.RESULTS: We discovered 11 associations between single-nucleotide polymorphisms and five distinct biomarkers at a study-wide P < 3.4 × 10(-7). Nine associations were novel: IL18: BIRC6, RAD17, MARVELD2; ferritin: F5; IGF binding protein 1: SERPING1, KLKB, GCKR, CELSR2, and heat shock 70-kDa protein 1B: CFH. Three of the identified loci (CELSR2, HNF1A, and GCKR) were significantly associated with T2D, of which the association with the CELSR2 locus has not been shown previously.CONCLUSION: The identified loci influence processes related to insulin signaling, cell communication, immune function, apoptosis, DNA repair, and oxidative stress, all of which could provide a rationale for novel diabetes therapeutic strategies.

AB - CONTEXT: Type 2 diabetes (T2D) prevalence is spiraling globally, and knowledge of its pathophysiological signatures is crucial for a better understanding and treatment of the disease.OBJECTIVE: We aimed to discover underlying coding genetic variants influencing fasting serum levels of nine biomarkers associated with T2D: adiponectin, C-reactive protein, ferritin, heat shock 70-kDa protein 1B, IGF binding protein 1 and IGF binding protein 2, IL-18, IL-2 receptor-α, and leptin.DESIGN AND PARTICIPANTS: A population-based sample of 6215 adult Danes was genotyped for 16 340 coding single-nucleotide polymorphisms and were tested for association with each biomarker. Identified loci were tested for association with T2D through a large-scale meta-analysis involving up to 17 024 T2D cases and up to 64 186 controls.RESULTS: We discovered 11 associations between single-nucleotide polymorphisms and five distinct biomarkers at a study-wide P < 3.4 × 10(-7). Nine associations were novel: IL18: BIRC6, RAD17, MARVELD2; ferritin: F5; IGF binding protein 1: SERPING1, KLKB, GCKR, CELSR2, and heat shock 70-kDa protein 1B: CFH. Three of the identified loci (CELSR2, HNF1A, and GCKR) were significantly associated with T2D, of which the association with the CELSR2 locus has not been shown previously.CONCLUSION: The identified loci influence processes related to insulin signaling, cell communication, immune function, apoptosis, DNA repair, and oxidative stress, all of which could provide a rationale for novel diabetes therapeutic strategies.

U2 - 10.1210/jc.2014-3677

DO - 10.1210/jc.2014-3677

M3 - Journal article

C2 - 25599387

VL - 100

SP - E664-71

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 4

ER -

ID: 135494309