IgG glycan patterns are associated with type 2 diabetes in independent European populations

Roosmarijn F H Lemmers; Marija Vilaj; Daniel Urda; Felix Agakov; Mirna Šimurina; Lucija Klaric; Igor Rudan; Harry Campbell; Caroline Hayward; Jim F Wilson; Aloysius G Lieverse; Olga Gornik; Eric J G Sijbrands; Gordan Lauc; Mandy van Hoek

doi:10.1016/j.bbagen.2017.06.020

IgG glycan patterns are associated with type 2 diabetes in independent European populations

Roosmarijn F H Lemmers, Marija Vilaj, Daniel Urda, Felix Agakov, Mirna Šimurina, Lucija Klaric, Igor Rudan, Harry Campbell, Caroline Hayward, Jim F Wilson, Aloysius G Lieverse, Olga Gornik, Eric J G Sijbrands, Gordan Lauc, Mandy van Hoek

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Abstract / Description of output

BACKGROUND: Type 2 diabetes results from interplay between genetic and acquired factors. Glycans on proteins reflect genetic, metabolic and environmental factors. However, associations of IgG glycans with type 2 diabetes have not been described. We compared IgG N-glycan patterns in type 2 diabetes with healthy subjects.

METHODS: In the DiaGene study, a population-based case-control study, (1886 cases and 854 controls) 58 IgG glycan traits were analyzed. Findings were replicated in the population-based CROATIA-Korcula-CROATIA-Vis-ORCADES studies (162 cases and 3162 controls), and meta-analyzed. AUCs of ROC-curves were calculated using 10-fold cross-validation for clinical characteristics, IgG glycans and their combination.

RESULTS: After correction for extensive clinical covariates, 5 IgG glycans and 13 derived traits significantly associated with type 2 diabetes in meta-analysis (after Bonferroni correction). Adding IgG glycans to age and sex increased the AUC from 0.542 to 0.734. Adding them to the extensive model did not substantially improve the AUC. The AUC for IgG glycans alone was 0.729.

CONCLUSIONS: Several IgG glycans and traits firmly associate with type 2 diabetes, reflecting a pro-inflammatory and biologically-aged state. IgG glycans showed limited improvement of AUCs. However, IgG glycans showed good prediction alone, indicating they may capture information of combined covariates. The associations found may yield insights in type 2 diabetes pathophysiology.

GENERAL SIGNIFICANCE: This work shows that IgG glycomic changes have biomarker potential and may yield important insights into pathophysiology of complex public health diseases, illustrated here for the first time in type 2 diabetes.

Original language	English
Pages (from-to)	2240-2249
Number of pages	10
Journal	BBA - Bioenergetics
Volume	1861
Issue number	9
Early online date	28 Jun 2017
DOIs	https://doi.org/10.1016/j.bbagen.2017.06.020
Publication status	Published - Sept 2017

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Journal Article

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10.1016/j.bbagen.2017.06.020

IgG glycan patterns are associated with type 2 diabetes in independent European populationsAccepted author manuscript, 181 KBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

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Lemmers, R. F. H., Vilaj, M., Urda, D., Agakov, F., Šimurina, M., Klaric, L., Rudan, I., Campbell, H., Hayward, C., Wilson, J. F., Lieverse, A. G., Gornik, O., Sijbrands, E. J. G., Lauc, G., & van Hoek, M. (2017). IgG glycan patterns are associated with type 2 diabetes in independent European populations. BBA - Bioenergetics, 1861(9), 2240-2249. https://doi.org/10.1016/j.bbagen.2017.06.020

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title = "IgG glycan patterns are associated with type 2 diabetes in independent European populations",

abstract = "BACKGROUND: Type 2 diabetes results from interplay between genetic and acquired factors. Glycans on proteins reflect genetic, metabolic and environmental factors. However, associations of IgG glycans with type 2 diabetes have not been described. We compared IgG N-glycan patterns in type 2 diabetes with healthy subjects.METHODS: In the DiaGene study, a population-based case-control study, (1886 cases and 854 controls) 58 IgG glycan traits were analyzed. Findings were replicated in the population-based CROATIA-Korcula-CROATIA-Vis-ORCADES studies (162 cases and 3162 controls), and meta-analyzed. AUCs of ROC-curves were calculated using 10-fold cross-validation for clinical characteristics, IgG glycans and their combination.RESULTS: After correction for extensive clinical covariates, 5 IgG glycans and 13 derived traits significantly associated with type 2 diabetes in meta-analysis (after Bonferroni correction). Adding IgG glycans to age and sex increased the AUC from 0.542 to 0.734. Adding them to the extensive model did not substantially improve the AUC. The AUC for IgG glycans alone was 0.729.CONCLUSIONS: Several IgG glycans and traits firmly associate with type 2 diabetes, reflecting a pro-inflammatory and biologically-aged state. IgG glycans showed limited improvement of AUCs. However, IgG glycans showed good prediction alone, indicating they may capture information of combined covariates. The associations found may yield insights in type 2 diabetes pathophysiology.GENERAL SIGNIFICANCE: This work shows that IgG glycomic changes have biomarker potential and may yield important insights into pathophysiology of complex public health diseases, illustrated here for the first time in type 2 diabetes.",

keywords = "Journal Article",

author = "Lemmers, {Roosmarijn F H} and Marija Vilaj and Daniel Urda and Felix Agakov and Mirna {\v S}imurina and Lucija Klaric and Igor Rudan and Harry Campbell and Caroline Hayward and Wilson, {Jim F} and Lieverse, {Aloysius G} and Olga Gornik and Sijbrands, {Eric J G} and Gordan Lauc and {van Hoek}, Mandy",

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Lemmers, RFH, Vilaj, M, Urda, D, Agakov, F, Šimurina, M, Klaric, L, Rudan, I , Campbell, H , Hayward, C , Wilson, JF, Lieverse, AG, Gornik, O, Sijbrands, EJG, Lauc, G & van Hoek, M 2017, 'IgG glycan patterns are associated with type 2 diabetes in independent European populations', BBA - Bioenergetics, vol. 1861, no. 9, pp. 2240-2249. https://doi.org/10.1016/j.bbagen.2017.06.020

TY - JOUR

T1 - IgG glycan patterns are associated with type 2 diabetes in independent European populations

AU - Lemmers, Roosmarijn F H

AU - Vilaj, Marija

AU - Urda, Daniel

AU - Agakov, Felix

AU - Šimurina, Mirna

AU - Klaric, Lucija

AU - Rudan, Igor

AU - Campbell, Harry

AU - Hayward, Caroline

AU - Wilson, Jim F

AU - Lieverse, Aloysius G

AU - Gornik, Olga

AU - Sijbrands, Eric J G

AU - Lauc, Gordan

AU - van Hoek, Mandy

PY - 2017/9

Y1 - 2017/9

N2 - BACKGROUND: Type 2 diabetes results from interplay between genetic and acquired factors. Glycans on proteins reflect genetic, metabolic and environmental factors. However, associations of IgG glycans with type 2 diabetes have not been described. We compared IgG N-glycan patterns in type 2 diabetes with healthy subjects.METHODS: In the DiaGene study, a population-based case-control study, (1886 cases and 854 controls) 58 IgG glycan traits were analyzed. Findings were replicated in the population-based CROATIA-Korcula-CROATIA-Vis-ORCADES studies (162 cases and 3162 controls), and meta-analyzed. AUCs of ROC-curves were calculated using 10-fold cross-validation for clinical characteristics, IgG glycans and their combination.RESULTS: After correction for extensive clinical covariates, 5 IgG glycans and 13 derived traits significantly associated with type 2 diabetes in meta-analysis (after Bonferroni correction). Adding IgG glycans to age and sex increased the AUC from 0.542 to 0.734. Adding them to the extensive model did not substantially improve the AUC. The AUC for IgG glycans alone was 0.729.CONCLUSIONS: Several IgG glycans and traits firmly associate with type 2 diabetes, reflecting a pro-inflammatory and biologically-aged state. IgG glycans showed limited improvement of AUCs. However, IgG glycans showed good prediction alone, indicating they may capture information of combined covariates. The associations found may yield insights in type 2 diabetes pathophysiology.GENERAL SIGNIFICANCE: This work shows that IgG glycomic changes have biomarker potential and may yield important insights into pathophysiology of complex public health diseases, illustrated here for the first time in type 2 diabetes.

AB - BACKGROUND: Type 2 diabetes results from interplay between genetic and acquired factors. Glycans on proteins reflect genetic, metabolic and environmental factors. However, associations of IgG glycans with type 2 diabetes have not been described. We compared IgG N-glycan patterns in type 2 diabetes with healthy subjects.METHODS: In the DiaGene study, a population-based case-control study, (1886 cases and 854 controls) 58 IgG glycan traits were analyzed. Findings were replicated in the population-based CROATIA-Korcula-CROATIA-Vis-ORCADES studies (162 cases and 3162 controls), and meta-analyzed. AUCs of ROC-curves were calculated using 10-fold cross-validation for clinical characteristics, IgG glycans and their combination.RESULTS: After correction for extensive clinical covariates, 5 IgG glycans and 13 derived traits significantly associated with type 2 diabetes in meta-analysis (after Bonferroni correction). Adding IgG glycans to age and sex increased the AUC from 0.542 to 0.734. Adding them to the extensive model did not substantially improve the AUC. The AUC for IgG glycans alone was 0.729.CONCLUSIONS: Several IgG glycans and traits firmly associate with type 2 diabetes, reflecting a pro-inflammatory and biologically-aged state. IgG glycans showed limited improvement of AUCs. However, IgG glycans showed good prediction alone, indicating they may capture information of combined covariates. The associations found may yield insights in type 2 diabetes pathophysiology.GENERAL SIGNIFICANCE: This work shows that IgG glycomic changes have biomarker potential and may yield important insights into pathophysiology of complex public health diseases, illustrated here for the first time in type 2 diabetes.

KW - Journal Article

U2 - 10.1016/j.bbagen.2017.06.020

DO - 10.1016/j.bbagen.2017.06.020

M3 - Article

C2 - 28668296

SN - 0005-2728

VL - 1861

SP - 2240

EP - 2249

JO - BBA - Bioenergetics

JF - BBA - Bioenergetics

IS - 9

ER -

IgG glycan patterns are associated with type 2 diabetes in independent European populations

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