Combined analysis of 19 common validated type 2 diabetes susceptibility gene variants shows moderate discriminative value and no evidence of gene-gene interaction

T Sparsø; N Grarup; C. Andreasen; A Albrechtsen; J Holmkvist; G Andersen; Torben Jørgensen; K Borch-Johnsen; A Sandbaek; T Lauritzen; S Madsbad; T Hansen; Oluf Pedersen; T Sparsø; N Grarup; C Andreasen; A Albrechtsen; J Holmkvist; G Andersen; T Jørgensen; K Borch-Johnsen; A Sandbaek; T Lauritzen; S Madsbad; T Hansen; O Pedersen

doi:10.1007/s00125-009-1362-3

Combined analysis of 19 common validated type 2 diabetes susceptibility gene variants shows moderate discriminative value and no evidence of gene-gene interaction

T Sparsø, N Grarup, C. Andreasen, A Albrechtsen, J Holmkvist, G Andersen, Torben Jørgensen, K Borch-Johnsen, A Sandbaek, T Lauritzen, S Madsbad, T Hansen, Oluf Pedersen, T Sparsø, N Grarup, C Andreasen, A Albrechtsen, J Holmkvist, G Andersen, T JørgensenK Borch-Johnsen, A Sandbaek, T Lauritzen, S Madsbad, T Hansen, O Pedersen

47 Citations (Scopus)

Abstract

AIMS/HYPOTHESIS: The list of validated type 2 diabetes susceptibility variants has recently been expanded from three to 19. The variants identified are common and have low penetrance in the general population. The aim of the study is to investigate the combined effect of the 19 variants by applying receiver operating characteristics (ROC) to demonstrate the discriminatory value between glucose-tolerant individuals and type 2 diabetes patients in a cross-sectional population of Danes. METHODS: The 19 variants were genotyped in three study populations: the population-based Inter99 study; the ADDITION study; and additional type 2 diabetic patients and glucose-tolerant individuals. The case-control studies involved 4,093 type 2 diabetic patients and 5,302 glucose-tolerant individuals. RESULTS: Single-variant analyses demonstrated allelic odds ratios ranging from 1.04 (95% CI 0.98-1.11) to 1.33 (95% CI 1.22-1.45). When combining the 19 variants, subgroups with extreme risk profiles showed a threefold difference in the risk of type 2 diabetes (lower 10% carriers with < or =15 risk alleles vs upper 10% carriers with > or =22 risk alleles, OR 2.93 (95% CI 2.38-3.62, p = 1.6 x 10(-25)). We calculated the area under a ROC curve to estimate the discrimination rate between glucose-tolerant individuals and type 2 diabetes patients based on the 19 variants. We found an area under the ROC curve of 0.60. Two-way gene-gene interaction showed few nominal interaction effects. CONCLUSIONS/INTERPRETATION: Combined analysis of the 19 validated variants enables detection of subgroups at substantially increased risk of type 2 diabetes; however, the discrimination between glucose-tolerant and type 2 diabetes individuals is still too inaccurate to achieve clinical value.

Original language	English
Journal	Diabetologia
Volume	52
Issue number	7
Pages (from-to)	1308-14
Number of pages	6
ISSN	0012-186X
DOIs	https://doi.org/10.1007/s00125-009-1362-3 https://doi.org/10.1007/s00125-009-1362-3
Publication status	Published - 2009

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Sparsø, T., Grarup, N., Andreasen, C., Albrechtsen, A., Holmkvist, J., Andersen, G., Jørgensen, T., Borch-Johnsen, K., Sandbaek, A., Lauritzen, T., Madsbad, S., Hansen, T., Pedersen, O., Sparsø, T., Grarup, N., Andreasen, C., Albrechtsen, A., Holmkvist, J., Andersen, G., ... Pedersen, O. (2009). Combined analysis of 19 common validated type 2 diabetes susceptibility gene variants shows moderate discriminative value and no evidence of gene-gene interaction. Diabetologia, 52(7), 1308-14. https://doi.org/10.1007/s00125-009-1362-3, https://doi.org/10.1007/s00125-009-1362-3

Sparsø, T, Grarup, N, Andreasen, C, Albrechtsen, A, Holmkvist, J, Andersen, G, Jørgensen, T, Borch-Johnsen, K, Sandbaek, A, Lauritzen, T, Madsbad, S, Hansen, T, Pedersen, O, Sparsø, T, Grarup, N, Andreasen, C, Albrechtsen, A, Holmkvist, J, Andersen, G, Jørgensen, T, Borch-Johnsen, K, Sandbaek, A, Lauritzen, T, Madsbad, S, Hansen, T & Pedersen, O 2009, 'Combined analysis of 19 common validated type 2 diabetes susceptibility gene variants shows moderate discriminative value and no evidence of gene-gene interaction', Diabetologia, vol. 52, no. 7, pp. 1308-14. https://doi.org/10.1007/s00125-009-1362-3, https://doi.org/10.1007/s00125-009-1362-3

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title = "Combined analysis of 19 common validated type 2 diabetes susceptibility gene variants shows moderate discriminative value and no evidence of gene-gene interaction",

abstract = "AIMS/HYPOTHESIS: The list of validated type 2 diabetes susceptibility variants has recently been expanded from three to 19. The variants identified are common and have low penetrance in the general population. The aim of the study is to investigate the combined effect of the 19 variants by applying receiver operating characteristics (ROC) to demonstrate the discriminatory value between glucose-tolerant individuals and type 2 diabetes patients in a cross-sectional population of Danes. METHODS: The 19 variants were genotyped in three study populations: the population-based Inter99 study; the ADDITION study; and additional type 2 diabetic patients and glucose-tolerant individuals. The case-control studies involved 4,093 type 2 diabetic patients and 5,302 glucose-tolerant individuals. RESULTS: Single-variant analyses demonstrated allelic odds ratios ranging from 1.04 (95% CI 0.98-1.11) to 1.33 (95% CI 1.22-1.45). When combining the 19 variants, subgroups with extreme risk profiles showed a threefold difference in the risk of type 2 diabetes (lower 10% carriers with < or =15 risk alleles vs upper 10% carriers with > or =22 risk alleles, OR 2.93 (95% CI 2.38-3.62, p = 1.6 x 10(-25)). We calculated the area under a ROC curve to estimate the discrimination rate between glucose-tolerant individuals and type 2 diabetes patients based on the 19 variants. We found an area under the ROC curve of 0.60. Two-way gene-gene interaction showed few nominal interaction effects. CONCLUSIONS/INTERPRETATION: Combined analysis of the 19 validated variants enables detection of subgroups at substantially increased risk of type 2 diabetes; however, the discrimination between glucose-tolerant and type 2 diabetes individuals is still too inaccurate to achieve clinical value.",

author = "T Spars{\o} and N Grarup and C. Andreasen and A Albrechtsen and J Holmkvist and G Andersen and Torben J{\o}rgensen and K Borch-Johnsen and A Sandbaek and T Lauritzen and S Madsbad and T Hansen and Oluf Pedersen and T Spars{\o} and N Grarup and C Andreasen and A Albrechtsen and J Holmkvist and G Andersen and T J{\o}rgensen and K Borch-Johnsen and A Sandbaek and T Lauritzen and S Madsbad and T Hansen and O Pedersen",

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T1 - Combined analysis of 19 common validated type 2 diabetes susceptibility gene variants shows moderate discriminative value and no evidence of gene-gene interaction

AU - Sparsø, T

AU - Grarup, N

AU - Andreasen, C.

AU - Albrechtsen, A

AU - Holmkvist, J

AU - Andersen, G

AU - Jørgensen, Torben

AU - Borch-Johnsen, K

AU - Sandbaek, A

AU - Lauritzen, T

AU - Madsbad, S

AU - Hansen, T

AU - Pedersen, Oluf

AU - Sparsø, T

AU - Grarup, N

AU - Andreasen, C

AU - Albrechtsen, A

AU - Holmkvist, J

AU - Andersen, G

AU - Jørgensen, T

AU - Borch-Johnsen, K

AU - Sandbaek, A

AU - Lauritzen, T

AU - Madsbad, S

AU - Hansen, T

AU - Pedersen, O

N1 - Cited By (since 1996): 1Export Date: 4 November 2009Source: Scopus

PY - 2009

Y1 - 2009

N2 - AIMS/HYPOTHESIS: The list of validated type 2 diabetes susceptibility variants has recently been expanded from three to 19. The variants identified are common and have low penetrance in the general population. The aim of the study is to investigate the combined effect of the 19 variants by applying receiver operating characteristics (ROC) to demonstrate the discriminatory value between glucose-tolerant individuals and type 2 diabetes patients in a cross-sectional population of Danes. METHODS: The 19 variants were genotyped in three study populations: the population-based Inter99 study; the ADDITION study; and additional type 2 diabetic patients and glucose-tolerant individuals. The case-control studies involved 4,093 type 2 diabetic patients and 5,302 glucose-tolerant individuals. RESULTS: Single-variant analyses demonstrated allelic odds ratios ranging from 1.04 (95% CI 0.98-1.11) to 1.33 (95% CI 1.22-1.45). When combining the 19 variants, subgroups with extreme risk profiles showed a threefold difference in the risk of type 2 diabetes (lower 10% carriers with < or =15 risk alleles vs upper 10% carriers with > or =22 risk alleles, OR 2.93 (95% CI 2.38-3.62, p = 1.6 x 10(-25)). We calculated the area under a ROC curve to estimate the discrimination rate between glucose-tolerant individuals and type 2 diabetes patients based on the 19 variants. We found an area under the ROC curve of 0.60. Two-way gene-gene interaction showed few nominal interaction effects. CONCLUSIONS/INTERPRETATION: Combined analysis of the 19 validated variants enables detection of subgroups at substantially increased risk of type 2 diabetes; however, the discrimination between glucose-tolerant and type 2 diabetes individuals is still too inaccurate to achieve clinical value.

AB - AIMS/HYPOTHESIS: The list of validated type 2 diabetes susceptibility variants has recently been expanded from three to 19. The variants identified are common and have low penetrance in the general population. The aim of the study is to investigate the combined effect of the 19 variants by applying receiver operating characteristics (ROC) to demonstrate the discriminatory value between glucose-tolerant individuals and type 2 diabetes patients in a cross-sectional population of Danes. METHODS: The 19 variants were genotyped in three study populations: the population-based Inter99 study; the ADDITION study; and additional type 2 diabetic patients and glucose-tolerant individuals. The case-control studies involved 4,093 type 2 diabetic patients and 5,302 glucose-tolerant individuals. RESULTS: Single-variant analyses demonstrated allelic odds ratios ranging from 1.04 (95% CI 0.98-1.11) to 1.33 (95% CI 1.22-1.45). When combining the 19 variants, subgroups with extreme risk profiles showed a threefold difference in the risk of type 2 diabetes (lower 10% carriers with < or =15 risk alleles vs upper 10% carriers with > or =22 risk alleles, OR 2.93 (95% CI 2.38-3.62, p = 1.6 x 10(-25)). We calculated the area under a ROC curve to estimate the discrimination rate between glucose-tolerant individuals and type 2 diabetes patients based on the 19 variants. We found an area under the ROC curve of 0.60. Two-way gene-gene interaction showed few nominal interaction effects. CONCLUSIONS/INTERPRETATION: Combined analysis of the 19 validated variants enables detection of subgroups at substantially increased risk of type 2 diabetes; however, the discrimination between glucose-tolerant and type 2 diabetes individuals is still too inaccurate to achieve clinical value.

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DO - 10.1007/s00125-009-1362-3

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C2 - 19404609

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JO - Diabetologia

JF - Diabetologia

IS - 7

ER -

Combined analysis of 19 common validated type 2 diabetes susceptibility gene variants shows moderate discriminative value and no evidence of gene-gene interaction

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