Genome-wide association study of circulating levels of glucagon during an oral glucose tolerance test

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Genome-wide association study of circulating levels of glucagon during an oral glucose tolerance test. / Jonsson, Anna; Stinson, Sara E.; Torekov, Signe S.; Clausen, Tine D.; Færch, Kristine; Kelstrup, Louise; Grarup, Niels; Mathiesen, Elisabeth R.; Damm, Peter; Witte, Daniel R.; Jørgensen, Marit E.; Pedersen, Oluf; Holst, Jens Juul; Hansen, Torben.

I: BMC Medical Genomics, Bind 14, 3, 2021.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Jonsson, A, Stinson, SE, Torekov, SS, Clausen, TD, Færch, K, Kelstrup, L, Grarup, N, Mathiesen, ER, Damm, P, Witte, DR, Jørgensen, ME, Pedersen, O, Holst, JJ & Hansen, T 2021, 'Genome-wide association study of circulating levels of glucagon during an oral glucose tolerance test', BMC Medical Genomics, bind 14, 3. https://doi.org/10.1186/s12920-020-00841-7

APA

Jonsson, A., Stinson, S. E., Torekov, S. S., Clausen, T. D., Færch, K., Kelstrup, L., Grarup, N., Mathiesen, E. R., Damm, P., Witte, D. R., Jørgensen, M. E., Pedersen, O., Holst, J. J., & Hansen, T. (2021). Genome-wide association study of circulating levels of glucagon during an oral glucose tolerance test. BMC Medical Genomics, 14, [3]. https://doi.org/10.1186/s12920-020-00841-7

Vancouver

Jonsson A, Stinson SE, Torekov SS, Clausen TD, Færch K, Kelstrup L o.a. Genome-wide association study of circulating levels of glucagon during an oral glucose tolerance test. BMC Medical Genomics. 2021;14. 3. https://doi.org/10.1186/s12920-020-00841-7

Author

Jonsson, Anna ; Stinson, Sara E. ; Torekov, Signe S. ; Clausen, Tine D. ; Færch, Kristine ; Kelstrup, Louise ; Grarup, Niels ; Mathiesen, Elisabeth R. ; Damm, Peter ; Witte, Daniel R. ; Jørgensen, Marit E. ; Pedersen, Oluf ; Holst, Jens Juul ; Hansen, Torben. / Genome-wide association study of circulating levels of glucagon during an oral glucose tolerance test. I: BMC Medical Genomics. 2021 ; Bind 14.

Bibtex

@article{06442fbcf9fb42b580d3c680dcb7a97f,
title = "Genome-wide association study of circulating levels of glucagon during an oral glucose tolerance test",
abstract = "Background: In order to explore the pathophysiology underlying type 2 diabetes we examined the impact of gene variants associated with type 2 diabetes on circulating levels of glucagon during an oral glucose tolerance test (OGTT). Furthermore, we performed a genome-wide association study (GWAS) aiming to identify novel genomic loci affecting plasma glucagon levels. Methods: Plasma levels of glucagon were examined in samples obtained at three time points during an OGTT; 0, 30 and 120 min, in two separate cohorts with a total of up to 1899 individuals. Cross-sectional analyses were performed separately in the two cohorts and the results were combined in a meta-analysis. Results: A known type 2 diabetes variant in EYA2 was significantly associated with higher plasma glucagon level at 30 min during the OGTT (Beta 0.145, SE 0.038, P = 1.2 × 10–4) corresponding to a 7.4% increase in plasma glucagon level per effect allele. In the GWAS, we identified a marker in the MARCH1 locus, which was genome-wide significantly associated with reduced suppression of glucagon during the first 30 min of the OGTT (Beta − 0.210, SE 0.037, P = 1.9 × 10–8), equivalent to 8.2% less suppression per effect allele. Nine additional independent markers, not previously associated with type 2 diabetes, showed suggestive associations with reduced glucagon suppression during the first 30 min of the OGTT (P < 1.0 × 10–5). Conclusions: A type 2 diabetes risk variant in the EYA2 locus was associated with higher plasma glucagon levels at 30 min. Ten additional variants were suggestively associated with reduced glucagon suppression without conferring increased type 2 diabetes risk.",
keywords = "Glucagon, GWAS, Type 2 diabetes",
author = "Anna Jonsson and Stinson, {Sara E.} and Torekov, {Signe S.} and Clausen, {Tine D.} and Kristine F{\ae}rch and Louise Kelstrup and Niels Grarup and Mathiesen, {Elisabeth R.} and Peter Damm and Witte, {Daniel R.} and J{\o}rgensen, {Marit E.} and Oluf Pedersen and Holst, {Jens Juul} and Torben Hansen",
year = "2021",
doi = "10.1186/s12920-020-00841-7",
language = "English",
volume = "14",
journal = "B M C Medical Genomics",
issn = "1755-8794",
publisher = "BioMed Central Ltd.",

}

RIS

TY - JOUR

T1 - Genome-wide association study of circulating levels of glucagon during an oral glucose tolerance test

AU - Jonsson, Anna

AU - Stinson, Sara E.

AU - Torekov, Signe S.

AU - Clausen, Tine D.

AU - Færch, Kristine

AU - Kelstrup, Louise

AU - Grarup, Niels

AU - Mathiesen, Elisabeth R.

AU - Damm, Peter

AU - Witte, Daniel R.

AU - Jørgensen, Marit E.

AU - Pedersen, Oluf

AU - Holst, Jens Juul

AU - Hansen, Torben

PY - 2021

Y1 - 2021

N2 - Background: In order to explore the pathophysiology underlying type 2 diabetes we examined the impact of gene variants associated with type 2 diabetes on circulating levels of glucagon during an oral glucose tolerance test (OGTT). Furthermore, we performed a genome-wide association study (GWAS) aiming to identify novel genomic loci affecting plasma glucagon levels. Methods: Plasma levels of glucagon were examined in samples obtained at three time points during an OGTT; 0, 30 and 120 min, in two separate cohorts with a total of up to 1899 individuals. Cross-sectional analyses were performed separately in the two cohorts and the results were combined in a meta-analysis. Results: A known type 2 diabetes variant in EYA2 was significantly associated with higher plasma glucagon level at 30 min during the OGTT (Beta 0.145, SE 0.038, P = 1.2 × 10–4) corresponding to a 7.4% increase in plasma glucagon level per effect allele. In the GWAS, we identified a marker in the MARCH1 locus, which was genome-wide significantly associated with reduced suppression of glucagon during the first 30 min of the OGTT (Beta − 0.210, SE 0.037, P = 1.9 × 10–8), equivalent to 8.2% less suppression per effect allele. Nine additional independent markers, not previously associated with type 2 diabetes, showed suggestive associations with reduced glucagon suppression during the first 30 min of the OGTT (P < 1.0 × 10–5). Conclusions: A type 2 diabetes risk variant in the EYA2 locus was associated with higher plasma glucagon levels at 30 min. Ten additional variants were suggestively associated with reduced glucagon suppression without conferring increased type 2 diabetes risk.

AB - Background: In order to explore the pathophysiology underlying type 2 diabetes we examined the impact of gene variants associated with type 2 diabetes on circulating levels of glucagon during an oral glucose tolerance test (OGTT). Furthermore, we performed a genome-wide association study (GWAS) aiming to identify novel genomic loci affecting plasma glucagon levels. Methods: Plasma levels of glucagon were examined in samples obtained at three time points during an OGTT; 0, 30 and 120 min, in two separate cohorts with a total of up to 1899 individuals. Cross-sectional analyses were performed separately in the two cohorts and the results were combined in a meta-analysis. Results: A known type 2 diabetes variant in EYA2 was significantly associated with higher plasma glucagon level at 30 min during the OGTT (Beta 0.145, SE 0.038, P = 1.2 × 10–4) corresponding to a 7.4% increase in plasma glucagon level per effect allele. In the GWAS, we identified a marker in the MARCH1 locus, which was genome-wide significantly associated with reduced suppression of glucagon during the first 30 min of the OGTT (Beta − 0.210, SE 0.037, P = 1.9 × 10–8), equivalent to 8.2% less suppression per effect allele. Nine additional independent markers, not previously associated with type 2 diabetes, showed suggestive associations with reduced glucagon suppression during the first 30 min of the OGTT (P < 1.0 × 10–5). Conclusions: A type 2 diabetes risk variant in the EYA2 locus was associated with higher plasma glucagon levels at 30 min. Ten additional variants were suggestively associated with reduced glucagon suppression without conferring increased type 2 diabetes risk.

KW - Glucagon

KW - GWAS

KW - Type 2 diabetes

U2 - 10.1186/s12920-020-00841-7

DO - 10.1186/s12920-020-00841-7

M3 - Journal article

C2 - 33407418

AN - SCOPUS:85098762248

VL - 14

JO - B M C Medical Genomics

JF - B M C Medical Genomics

SN - 1755-8794

M1 - 3

ER -

ID: 256896010