Genetic Variant SLC2A2 Is Associated with Risk of Cardiovascular Disease - Assessing the Individual and Cumulative Effect of 46 Type 2 Diabetes Related Genetic Variants

Anders Borglykke; Niels Grarup; Thomas Sparsø; Allan Linneberg; Mogens Fenger; Jørgen Jeppesen; Torben Hansen; Oluf Pedersen; Torben Jørgensen

doi:10.1371/journal.pone.0050418

Genetic Variant SLC2A2 Is Associated with Risk of Cardiovascular Disease - Assessing the Individual and Cumulative Effect of 46 Type 2 Diabetes Related Genetic Variants

Anders Borglykke, Niels Grarup, Thomas Sparsø, Allan Linneberg, Mogens Fenger, Jørgen Jeppesen, Torben Hansen, Oluf Pedersen, Torben Jørgensen

13 Citations (Scopus)

Abstract

Aim: To assess the individual and combined effect of 46 type 2 diabetes related risk alleles on incidence of a composite CVD endpoint. Methods: Data from the first Danish MONICA study (N = 3523) and the Inter99 study (N = 6049) was used. Using Cox proportional hazard regression the individual effect of each risk allele on incident CVD was analyzed. Risk was presented as hazard ratios (HR) per risk allele. Results: During 80,859 person years 1441 incident cases of CVD (fatal and non-fatal) occurred in the MONICA study. In Inter99 942 incident cases were observed during 61,239 person years. In the Danish MONICA study four gene variants were significantly associated with incident CVD independently of known diabetes status at baseline; SLC2A2 rs11920090 (HR 1.147, 95% CI 1.027-1.283, P = 0.0154), C2CD4A rs7172432 (1.112, 1.027-1.205, P = 0.0089), GCKR rs780094 (1.094, 1.007-1.188, P = 0.0335) and C2CD4B rs11071657 (1.092, 1.007-1.183, P = 0.0323). The genetic score was significantly associated with increased risk of CVD (1.025, 1.010-1.041, P = 0.0016). In Inter99 two gene variants were associated with risk of CVD independently of diabetes; SLC2A2 (HR 1.180, 95% CI 1.038-1.341 P = 0.0116) and FTO (0.909, 0.827-0.998, P = 0.0463). Analysing the two populations together we found SLC2A2 rs11920090 (HR 1.164, 95% CI 1.070-1.267, P = 0.0004) meeting the Bonferroni corrected threshold for significance. GCKR rs780094 (1.076, 1.010-1.146, P = 0.0229), C2CD4B rs11071657 (1.067, 1.003-1.135, P = 0.0385) and NOTCH2 rs10923931 (1.104 (1.001; 1.217, P = 0.0481) were found associated with CVD without meeting the corrected threshold. The genetic score was significantly associated with increased risk of CVD (1.018, 1.006-1.031, P = 0.0043). Conclusions: This study showed that out of the 46 genetic variants examined only the minor risk allele of SLC2A2 rs11920090 was significantly (P = 0.0005) associated with a composite endpoint of incident CVD below the threshold for statistical significance corrected for multiple testing. This potential pathway needs further exploration.

Original language	English
Journal	P L o S One
Volume	7
Issue number	11
Pages (from-to)	e50418
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0050418
Publication status	Published - 21 Nov 2012

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10.1371/journal.pone.0050418

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Borglykke, A., Grarup, N., Sparsø, T., Linneberg, A., Fenger, M., Jeppesen, J., Hansen, T., Pedersen, O., & Jørgensen, T. (2012). Genetic Variant SLC2A2 Is Associated with Risk of Cardiovascular Disease - Assessing the Individual and Cumulative Effect of 46 Type 2 Diabetes Related Genetic Variants. P L o S One, 7(11), e50418. https://doi.org/10.1371/journal.pone.0050418

Genetic Variant SLC2A2 Is Associated with Risk of Cardiovascular Disease - Assessing the Individual and Cumulative Effect of 46 Type 2 Diabetes Related Genetic Variants. / Borglykke, Anders; Grarup, Niels; Sparsø, Thomas et al.

In: P L o S One, Vol. 7, No. 11, 21.11.2012, p. e50418.

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

Borglykke, A, Grarup, N, Sparsø, T, Linneberg, A, Fenger, M, Jeppesen, J, Hansen, T , Pedersen, O & Jørgensen, T 2012, 'Genetic Variant SLC2A2 Is Associated with Risk of Cardiovascular Disease - Assessing the Individual and Cumulative Effect of 46 Type 2 Diabetes Related Genetic Variants', P L o S One, vol. 7, no. 11, pp. e50418. https://doi.org/10.1371/journal.pone.0050418

@article{9b507372a95f4a0a9d12d5e5c6252a17,

title = "Genetic Variant SLC2A2 Is Associated with Risk of Cardiovascular Disease - Assessing the Individual and Cumulative Effect of 46 Type 2 Diabetes Related Genetic Variants",

abstract = "Aim: To assess the individual and combined effect of 46 type 2 diabetes related risk alleles on incidence of a composite CVD endpoint. Methods: Data from the first Danish MONICA study (N = 3523) and the Inter99 study (N = 6049) was used. Using Cox proportional hazard regression the individual effect of each risk allele on incident CVD was analyzed. Risk was presented as hazard ratios (HR) per risk allele. Results: During 80,859 person years 1441 incident cases of CVD (fatal and non-fatal) occurred in the MONICA study. In Inter99 942 incident cases were observed during 61,239 person years. In the Danish MONICA study four gene variants were significantly associated with incident CVD independently of known diabetes status at baseline; SLC2A2 rs11920090 (HR 1.147, 95% CI 1.027-1.283, P = 0.0154), C2CD4A rs7172432 (1.112, 1.027-1.205, P = 0.0089), GCKR rs780094 (1.094, 1.007-1.188, P = 0.0335) and C2CD4B rs11071657 (1.092, 1.007-1.183, P = 0.0323). The genetic score was significantly associated with increased risk of CVD (1.025, 1.010-1.041, P = 0.0016). In Inter99 two gene variants were associated with risk of CVD independently of diabetes; SLC2A2 (HR 1.180, 95% CI 1.038-1.341 P = 0.0116) and FTO (0.909, 0.827-0.998, P = 0.0463). Analysing the two populations together we found SLC2A2 rs11920090 (HR 1.164, 95% CI 1.070-1.267, P = 0.0004) meeting the Bonferroni corrected threshold for significance. GCKR rs780094 (1.076, 1.010-1.146, P = 0.0229), C2CD4B rs11071657 (1.067, 1.003-1.135, P = 0.0385) and NOTCH2 rs10923931 (1.104 (1.001; 1.217, P = 0.0481) were found associated with CVD without meeting the corrected threshold. The genetic score was significantly associated with increased risk of CVD (1.018, 1.006-1.031, P = 0.0043). Conclusions: This study showed that out of the 46 genetic variants examined only the minor risk allele of SLC2A2 rs11920090 was significantly (P = 0.0005) associated with a composite endpoint of incident CVD below the threshold for statistical significance corrected for multiple testing. This potential pathway needs further exploration.",

author = "Anders Borglykke and Niels Grarup and Thomas Spars{\o} and Allan Linneberg and Mogens Fenger and J{\o}rgen Jeppesen and Torben Hansen and Oluf Pedersen and Torben J{\o}rgensen",

year = "2012",

month = nov,

day = "21",

doi = "10.1371/journal.pone.0050418",

language = "English",

volume = "7",

pages = "e50418",

journal = "PLoS Computational Biology",

issn = "1932-6203",

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TY - JOUR

T1 - Genetic Variant SLC2A2 Is Associated with Risk of Cardiovascular Disease - Assessing the Individual and Cumulative Effect of 46 Type 2 Diabetes Related Genetic Variants

AU - Borglykke, Anders

AU - Grarup, Niels

AU - Sparsø, Thomas

AU - Linneberg, Allan

AU - Fenger, Mogens

AU - Jeppesen, Jørgen

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Jørgensen, Torben

PY - 2012/11/21

Y1 - 2012/11/21

N2 - Aim: To assess the individual and combined effect of 46 type 2 diabetes related risk alleles on incidence of a composite CVD endpoint. Methods: Data from the first Danish MONICA study (N = 3523) and the Inter99 study (N = 6049) was used. Using Cox proportional hazard regression the individual effect of each risk allele on incident CVD was analyzed. Risk was presented as hazard ratios (HR) per risk allele. Results: During 80,859 person years 1441 incident cases of CVD (fatal and non-fatal) occurred in the MONICA study. In Inter99 942 incident cases were observed during 61,239 person years. In the Danish MONICA study four gene variants were significantly associated with incident CVD independently of known diabetes status at baseline; SLC2A2 rs11920090 (HR 1.147, 95% CI 1.027-1.283, P = 0.0154), C2CD4A rs7172432 (1.112, 1.027-1.205, P = 0.0089), GCKR rs780094 (1.094, 1.007-1.188, P = 0.0335) and C2CD4B rs11071657 (1.092, 1.007-1.183, P = 0.0323). The genetic score was significantly associated with increased risk of CVD (1.025, 1.010-1.041, P = 0.0016). In Inter99 two gene variants were associated with risk of CVD independently of diabetes; SLC2A2 (HR 1.180, 95% CI 1.038-1.341 P = 0.0116) and FTO (0.909, 0.827-0.998, P = 0.0463). Analysing the two populations together we found SLC2A2 rs11920090 (HR 1.164, 95% CI 1.070-1.267, P = 0.0004) meeting the Bonferroni corrected threshold for significance. GCKR rs780094 (1.076, 1.010-1.146, P = 0.0229), C2CD4B rs11071657 (1.067, 1.003-1.135, P = 0.0385) and NOTCH2 rs10923931 (1.104 (1.001; 1.217, P = 0.0481) were found associated with CVD without meeting the corrected threshold. The genetic score was significantly associated with increased risk of CVD (1.018, 1.006-1.031, P = 0.0043). Conclusions: This study showed that out of the 46 genetic variants examined only the minor risk allele of SLC2A2 rs11920090 was significantly (P = 0.0005) associated with a composite endpoint of incident CVD below the threshold for statistical significance corrected for multiple testing. This potential pathway needs further exploration.

AB - Aim: To assess the individual and combined effect of 46 type 2 diabetes related risk alleles on incidence of a composite CVD endpoint. Methods: Data from the first Danish MONICA study (N = 3523) and the Inter99 study (N = 6049) was used. Using Cox proportional hazard regression the individual effect of each risk allele on incident CVD was analyzed. Risk was presented as hazard ratios (HR) per risk allele. Results: During 80,859 person years 1441 incident cases of CVD (fatal and non-fatal) occurred in the MONICA study. In Inter99 942 incident cases were observed during 61,239 person years. In the Danish MONICA study four gene variants were significantly associated with incident CVD independently of known diabetes status at baseline; SLC2A2 rs11920090 (HR 1.147, 95% CI 1.027-1.283, P = 0.0154), C2CD4A rs7172432 (1.112, 1.027-1.205, P = 0.0089), GCKR rs780094 (1.094, 1.007-1.188, P = 0.0335) and C2CD4B rs11071657 (1.092, 1.007-1.183, P = 0.0323). The genetic score was significantly associated with increased risk of CVD (1.025, 1.010-1.041, P = 0.0016). In Inter99 two gene variants were associated with risk of CVD independently of diabetes; SLC2A2 (HR 1.180, 95% CI 1.038-1.341 P = 0.0116) and FTO (0.909, 0.827-0.998, P = 0.0463). Analysing the two populations together we found SLC2A2 rs11920090 (HR 1.164, 95% CI 1.070-1.267, P = 0.0004) meeting the Bonferroni corrected threshold for significance. GCKR rs780094 (1.076, 1.010-1.146, P = 0.0229), C2CD4B rs11071657 (1.067, 1.003-1.135, P = 0.0385) and NOTCH2 rs10923931 (1.104 (1.001; 1.217, P = 0.0481) were found associated with CVD without meeting the corrected threshold. The genetic score was significantly associated with increased risk of CVD (1.018, 1.006-1.031, P = 0.0043). Conclusions: This study showed that out of the 46 genetic variants examined only the minor risk allele of SLC2A2 rs11920090 was significantly (P = 0.0005) associated with a composite endpoint of incident CVD below the threshold for statistical significance corrected for multiple testing. This potential pathway needs further exploration.

U2 - 10.1371/journal.pone.0050418

DO - 10.1371/journal.pone.0050418

M3 - Journal article

C2 - 23185617

SN - 1932-6203

VL - 7

SP - e50418

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 11

ER -

Genetic Variant SLC2A2 Is Associated with Risk of Cardiovascular Disease - Assessing the Individual and Cumulative Effect of 46 Type 2 Diabetes Related Genetic Variants

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