Investigation of gene–diet interactions in the incretin system and risk of type 2 diabetes: the EPIC-InterAct study

The InterAct Consortium

doi:10.1007/s00125-016-4090-5

Investigation of gene–diet interactions in the incretin system and risk of type 2 diabetes: the EPIC-InterAct study

The InterAct Consortium

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Abstract

Aims/hypothesis: The gut incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) have a major role in the pathophysiology of type 2 diabetes. Specific genetic and dietary factors have been found to influence the release and action of incretins. We examined the effect of interactions between seven incretin-related genetic variants in GIPR, KCNQ1, TCF7L2 and WFS1 and dietary components (whey-containing dairy, cereal fibre, coffee and olive oil) on the risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study.

Methods: The current case-cohort study included 8086 incident type 2 diabetes cases and a representative subcohort of 11,035 participants (median follow-up: 12.5 years). Prentice-weighted Cox proportional hazard regression models were used to investigate the associations and interactions between the dietary factors and genes in relation to the risk of type 2 diabetes.

Results: An interaction (p = 0.048) between TCF7L2 variants and coffee intake was apparent, with an inverse association between coffee and type 2 diabetes present among carriers of the diabetes risk allele (T) in rs12255372 (GG: HR 0.99 [95% CI 0.97, 1.02] per cup of coffee; GT: HR 0.96 [95% CI 0.93, 0.98]); and TT: HR 0.93 [95% CI 0.88, 0.98]). In addition, an interaction (p = 0.005) between an incretin-specific genetic risk score and coffee was observed, again with a stronger inverse association with coffee in carriers with more risk alleles (0–3 risk alleles: HR 0.99 [95% CI 0.94, 1.04]; 7–10 risk alleles: HR 0.95 [95% CI 0.90, 0.99]). None of these associations were statistically significant after correction for multiple testing.

Conclusions/interpretation: Our large-scale case-cohort study provides some evidence for a possible interaction of TCF7L2 variants and an incretin-specific genetic risk score with coffee consumption in relation to the risk of type 2 diabetes. Further large-scale studies and/or meta-analyses are needed to confirm these interactions in other populations.

Original language	English
Pages (from-to)	2613-2621
Number of pages	9
Journal	Diabetologia
Volume	59
Issue number	12
Early online date	13 Sept 2016
DOIs	https://doi.org/10.1007/s00125-016-4090-5
Publication status	Published - 01 Dec 2016
Externally published	Yes

Bibliographical note

Funding Information:
Funding for the InterAct project was provided by the EU FP6 programme (grant no. LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following agencies: YTvdS: Dutch research council (NWO-ZonMW; grant no. 40-00812-98-10040), verification of diabetes cases in EPIC-NL was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; EA: Health Research Fund (FIS) of the Spanish Ministry of Health, Navarre Regional Government and CIBER Epidemiología y Salud Pública (CIBERESP); GB: Spanish Ministry of Health (ISCIII RETICC RD 06/0020/0091) and the Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation; RK: German Cancer Aid, German Ministry of Research (BMBF); TJK: Cancer Research UK; KTK: Medical Research Council UK, Cancer Research UK; CN: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (no. 6236); PMN: Swedish Research Council; KO: Danish Cancer Society; OR: The Västerboten County Council; YTvdS, IS, AMWS and DLvdA: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; AT: Danish Cancer Society; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; ER: Imperial College Biomedical Research Centre.

Funding Information:
We thank all EPIC participants and staff for their contribution to the study. We thank N. Kerrison (MRC Epidemiology Unit, Cambridge, UK) for managing the data for the InterAct Project. The InterAct Consortium list of authors is shown in the electronic supplementary material (ESM ). Funding for the InterAct project was provided by the EU FP6 programme (grant no. LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following agencies: YTvdS: Dutch research council (NWO-ZonMW; grant no. 40-00812-98-10040), verification of diabetes cases in EPIC-NL was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; EA: Health Research Fund (FIS) of the Spanish Ministry of Health, Navarre Regional Government and CIBER Epidemiolog?a y Salud P?blica (CIBERESP); GB: Spanish Ministry of Health (ISCIII RETICC RD 06/0020/0091) and the Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation; RK: German Cancer Aid, German Ministry of Research (BMBF); TJK: Cancer Research UK; KTK: Medical Research Council UK, Cancer Research UK; CN: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (no. 6236); PMN: Swedish Research Council; KO: Danish Cancer Society; OR: The V?sterboten County Council; YTvdS, IS, AMWS and DLvdA: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; AT: Danish Cancer Society; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; ER: Imperial College Biomedical Research Centre.

Publisher Copyright:
© 2016, The Author(s).

Keywords

Coffee
Dairy
Fibre
Gene–environment interaction
GIPR
Incretins
KCNQ1
Olive oil
TCF7L2
WFS1

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00125-016-4090-5Licence: CC BY

Investigation of gene–diet interactions in the incretin system and risk of type 2 diabetes: the EPIC-InterAct study
Copyright 2016 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 330 KBLicence: CC BY

Cite this

@article{57c8a55d7be8446293fd948c9d5dc0a1,

title = "Investigation of gene–diet interactions in the incretin system and risk of type 2 diabetes: the EPIC-InterAct study",

abstract = "Aims/hypothesis: The gut incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) have a major role in the pathophysiology of type 2 diabetes. Specific genetic and dietary factors have been found to influence the release and action of incretins. We examined the effect of interactions between seven incretin-related genetic variants in GIPR, KCNQ1, TCF7L2 and WFS1 and dietary components (whey-containing dairy, cereal fibre, coffee and olive oil) on the risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study. Methods: The current case-cohort study included 8086 incident type 2 diabetes cases and a representative subcohort of 11,035 participants (median follow-up: 12.5 years). Prentice-weighted Cox proportional hazard regression models were used to investigate the associations and interactions between the dietary factors and genes in relation to the risk of type 2 diabetes. Results: An interaction (p = 0.048) between TCF7L2 variants and coffee intake was apparent, with an inverse association between coffee and type 2 diabetes present among carriers of the diabetes risk allele (T) in rs12255372 (GG: HR 0.99 [95% CI 0.97, 1.02] per cup of coffee; GT: HR 0.96 [95% CI 0.93, 0.98]); and TT: HR 0.93 [95% CI 0.88, 0.98]). In addition, an interaction (p = 0.005) between an incretin-specific genetic risk score and coffee was observed, again with a stronger inverse association with coffee in carriers with more risk alleles (0–3 risk alleles: HR 0.99 [95% CI 0.94, 1.04]; 7–10 risk alleles: HR 0.95 [95% CI 0.90, 0.99]). None of these associations were statistically significant after correction for multiple testing. Conclusions/interpretation: Our large-scale case-cohort study provides some evidence for a possible interaction of TCF7L2 variants and an incretin-specific genetic risk score with coffee consumption in relation to the risk of type 2 diabetes. Further large-scale studies and/or meta-analyses are needed to confirm these interactions in other populations.",

keywords = "Coffee, Dairy, Fibre, Gene–environment interaction, GIPR, Incretins, KCNQ1, Olive oil, TCF7L2, WFS1",

author = "Alexandros Heraclides and Karina Meidtner and Brian Buijsse and {van der Schouw}, {Yvonne T.} and Ivonne Sluijs and {van der A}, {Daphne L.} and Anneleen Kuijsten and Antonio Agudo and Eva Ardanaz and Heiner Boeing and Feskens, {Edith J.M.} and Diana Gavrila and Verena Katzke and Key, {Timothy J.} and Tilman K{\"u}hn and Vittorio Krogh and Cecilie Kyr{\o} and Elena Molina-Portillo and Mortensen, {Lotte Maxild} and Nilsson, {Peter M.} and Kim Overvad and Domenico Palli and Salvatore Panico and Fulvio Ricceri and Rosario Tumino and Forouhi, {Nita G.} and Claudia Langenberg and Robert Scott and Franks, {Paul W.} and Schulze, {Matthias B.} and Elio Riboli and Wareham, {Nicholas J.} and {The InterAct Consortium}",

note = "Funding Information: Funding for the InterAct project was provided by the EU FP6 programme (grant no. LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following agencies: YTvdS: Dutch research council (NWO-ZonMW; grant no. 40-00812-98-10040), verification of diabetes cases in EPIC-NL was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; EA: Health Research Fund (FIS) of the Spanish Ministry of Health, Navarre Regional Government and CIBER Epidemiolog{\'i}a y Salud P{\'u}blica (CIBERESP); GB: Spanish Ministry of Health (ISCIII RETICC RD 06/0020/0091) and the Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation; RK: German Cancer Aid, German Ministry of Research (BMBF); TJK: Cancer Research UK; KTK: Medical Research Council UK, Cancer Research UK; CN: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (no. 6236); PMN: Swedish Research Council; KO: Danish Cancer Society; OR: The V{\"a}sterboten County Council; YTvdS, IS, AMWS and DLvdA: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; AT: Danish Cancer Society; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; ER: Imperial College Biomedical Research Centre. Funding Information: We thank all EPIC participants and staff for their contribution to the study. We thank N. Kerrison (MRC Epidemiology Unit, Cambridge, UK) for managing the data for the InterAct Project. The InterAct Consortium list of authors is shown in the electronic supplementary material (ESM ). Funding for the InterAct project was provided by the EU FP6 programme (grant no. LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following agencies: YTvdS: Dutch research council (NWO-ZonMW; grant no. 40-00812-98-10040), verification of diabetes cases in EPIC-NL was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; EA: Health Research Fund (FIS) of the Spanish Ministry of Health, Navarre Regional Government and CIBER Epidemiolog?a y Salud P?blica (CIBERESP); GB: Spanish Ministry of Health (ISCIII RETICC RD 06/0020/0091) and the Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation; RK: German Cancer Aid, German Ministry of Research (BMBF); TJK: Cancer Research UK; KTK: Medical Research Council UK, Cancer Research UK; CN: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (no. 6236); PMN: Swedish Research Council; KO: Danish Cancer Society; OR: The V?sterboten County Council; YTvdS, IS, AMWS and DLvdA: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; AT: Danish Cancer Society; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; ER: Imperial College Biomedical Research Centre. Publisher Copyright: {\textcopyright} 2016, The Author(s).",

year = "2016",

month = dec,

day = "1",

doi = "10.1007/s00125-016-4090-5",

language = "English",

volume = "59",

pages = "2613--2621",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer Verlag",

number = "12",

}

TY - JOUR

T1 - Investigation of gene–diet interactions in the incretin system and risk of type 2 diabetes: the EPIC-InterAct study

AU - Heraclides, Alexandros

AU - Meidtner, Karina

AU - Buijsse, Brian

AU - van der Schouw, Yvonne T.

AU - Sluijs, Ivonne

AU - van der A, Daphne L.

AU - Kuijsten, Anneleen

AU - Agudo, Antonio

AU - Ardanaz, Eva

AU - Boeing, Heiner

AU - Feskens, Edith J.M.

AU - Gavrila, Diana

AU - Katzke, Verena

AU - Key, Timothy J.

AU - Kühn, Tilman

AU - Krogh, Vittorio

AU - Kyrø, Cecilie

AU - Molina-Portillo, Elena

AU - Mortensen, Lotte Maxild

AU - Nilsson, Peter M.

AU - Overvad, Kim

AU - Palli, Domenico

AU - Panico, Salvatore

AU - Ricceri, Fulvio

AU - Tumino, Rosario

AU - Forouhi, Nita G.

AU - Langenberg, Claudia

AU - Scott, Robert

AU - Franks, Paul W.

AU - Schulze, Matthias B.

AU - Riboli, Elio

AU - Wareham, Nicholas J.

AU - The InterAct Consortium

N1 - Funding Information: Funding for the InterAct project was provided by the EU FP6 programme (grant no. LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following agencies: YTvdS: Dutch research council (NWO-ZonMW; grant no. 40-00812-98-10040), verification of diabetes cases in EPIC-NL was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; EA: Health Research Fund (FIS) of the Spanish Ministry of Health, Navarre Regional Government and CIBER Epidemiología y Salud Pública (CIBERESP); GB: Spanish Ministry of Health (ISCIII RETICC RD 06/0020/0091) and the Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation; RK: German Cancer Aid, German Ministry of Research (BMBF); TJK: Cancer Research UK; KTK: Medical Research Council UK, Cancer Research UK; CN: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (no. 6236); PMN: Swedish Research Council; KO: Danish Cancer Society; OR: The Västerboten County Council; YTvdS, IS, AMWS and DLvdA: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; AT: Danish Cancer Society; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; ER: Imperial College Biomedical Research Centre. Funding Information: We thank all EPIC participants and staff for their contribution to the study. We thank N. Kerrison (MRC Epidemiology Unit, Cambridge, UK) for managing the data for the InterAct Project. The InterAct Consortium list of authors is shown in the electronic supplementary material (ESM ). Funding for the InterAct project was provided by the EU FP6 programme (grant no. LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following agencies: YTvdS: Dutch research council (NWO-ZonMW; grant no. 40-00812-98-10040), verification of diabetes cases in EPIC-NL was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; EA: Health Research Fund (FIS) of the Spanish Ministry of Health, Navarre Regional Government and CIBER Epidemiolog?a y Salud P?blica (CIBERESP); GB: Spanish Ministry of Health (ISCIII RETICC RD 06/0020/0091) and the Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation; RK: German Cancer Aid, German Ministry of Research (BMBF); TJK: Cancer Research UK; KTK: Medical Research Council UK, Cancer Research UK; CN: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (no. 6236); PMN: Swedish Research Council; KO: Danish Cancer Society; OR: The V?sterboten County Council; YTvdS, IS, AMWS and DLvdA: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; AT: Danish Cancer Society; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; ER: Imperial College Biomedical Research Centre. Publisher Copyright: © 2016, The Author(s).

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Aims/hypothesis: The gut incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) have a major role in the pathophysiology of type 2 diabetes. Specific genetic and dietary factors have been found to influence the release and action of incretins. We examined the effect of interactions between seven incretin-related genetic variants in GIPR, KCNQ1, TCF7L2 and WFS1 and dietary components (whey-containing dairy, cereal fibre, coffee and olive oil) on the risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study. Methods: The current case-cohort study included 8086 incident type 2 diabetes cases and a representative subcohort of 11,035 participants (median follow-up: 12.5 years). Prentice-weighted Cox proportional hazard regression models were used to investigate the associations and interactions between the dietary factors and genes in relation to the risk of type 2 diabetes. Results: An interaction (p = 0.048) between TCF7L2 variants and coffee intake was apparent, with an inverse association between coffee and type 2 diabetes present among carriers of the diabetes risk allele (T) in rs12255372 (GG: HR 0.99 [95% CI 0.97, 1.02] per cup of coffee; GT: HR 0.96 [95% CI 0.93, 0.98]); and TT: HR 0.93 [95% CI 0.88, 0.98]). In addition, an interaction (p = 0.005) between an incretin-specific genetic risk score and coffee was observed, again with a stronger inverse association with coffee in carriers with more risk alleles (0–3 risk alleles: HR 0.99 [95% CI 0.94, 1.04]; 7–10 risk alleles: HR 0.95 [95% CI 0.90, 0.99]). None of these associations were statistically significant after correction for multiple testing. Conclusions/interpretation: Our large-scale case-cohort study provides some evidence for a possible interaction of TCF7L2 variants and an incretin-specific genetic risk score with coffee consumption in relation to the risk of type 2 diabetes. Further large-scale studies and/or meta-analyses are needed to confirm these interactions in other populations.

AB - Aims/hypothesis: The gut incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) have a major role in the pathophysiology of type 2 diabetes. Specific genetic and dietary factors have been found to influence the release and action of incretins. We examined the effect of interactions between seven incretin-related genetic variants in GIPR, KCNQ1, TCF7L2 and WFS1 and dietary components (whey-containing dairy, cereal fibre, coffee and olive oil) on the risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study. Methods: The current case-cohort study included 8086 incident type 2 diabetes cases and a representative subcohort of 11,035 participants (median follow-up: 12.5 years). Prentice-weighted Cox proportional hazard regression models were used to investigate the associations and interactions between the dietary factors and genes in relation to the risk of type 2 diabetes. Results: An interaction (p = 0.048) between TCF7L2 variants and coffee intake was apparent, with an inverse association between coffee and type 2 diabetes present among carriers of the diabetes risk allele (T) in rs12255372 (GG: HR 0.99 [95% CI 0.97, 1.02] per cup of coffee; GT: HR 0.96 [95% CI 0.93, 0.98]); and TT: HR 0.93 [95% CI 0.88, 0.98]). In addition, an interaction (p = 0.005) between an incretin-specific genetic risk score and coffee was observed, again with a stronger inverse association with coffee in carriers with more risk alleles (0–3 risk alleles: HR 0.99 [95% CI 0.94, 1.04]; 7–10 risk alleles: HR 0.95 [95% CI 0.90, 0.99]). None of these associations were statistically significant after correction for multiple testing. Conclusions/interpretation: Our large-scale case-cohort study provides some evidence for a possible interaction of TCF7L2 variants and an incretin-specific genetic risk score with coffee consumption in relation to the risk of type 2 diabetes. Further large-scale studies and/or meta-analyses are needed to confirm these interactions in other populations.

KW - Coffee

KW - Dairy

KW - Fibre

KW - Gene–environment interaction

KW - GIPR

KW - Incretins

KW - KCNQ1

KW - Olive oil

KW - TCF7L2

KW - WFS1

U2 - 10.1007/s00125-016-4090-5

DO - 10.1007/s00125-016-4090-5

M3 - Article

C2 - 27623947

AN - SCOPUS:84987619279

SN - 0012-186X

VL - 59

SP - 2613

EP - 2621

JO - Diabetologia

JF - Diabetologia

IS - 12

ER -

Investigation of gene–diet interactions in the incretin system and risk of type 2 diabetes: the EPIC-InterAct study

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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