Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus

CARDIOGRAMplusC4D Steering Committee; Natalie R. Van Zuydam; Claes Ladenvall; Benjamin F. Voight; Rona J. Strawbridge; Juan Fernandez-Tajes; N. William Rayner; Neil R. Robertson; Anubha Mahajan; Efthymia Vlachopoulou; Anuj Goel; Marcus E. Kleber; Christopher P. Nelson; Lydia Coulter Kwee; Tõnu Esko; Evelin Mihailov; Reedik Mägi; Lili Milani; Krista Fischer; Stavroula Kanoni; Jitender Kumar; Ci Song; Jaana A. Hartiala; Nancy L. Pedersen; Markus Perola; Christian Gieger; Annette Peters; Liming Qu; Sara M. Willems; Alex S. F. Doney; Andrew D. Morris; Yan Zheng; Giorgio Sesti; Frank B. Hu; Lu Qi; Markku Laakso; Unnur Thorsteinsdottir; Harald Grallert; Cornelia Van Duijn; Muredach P. Reilly; Erik Ingelsson; Panos Deloukas; Sek Kathiresan; Andres Metspalu; Svati H. Shah; Juha Sinisalo; Veikko Salomaa; Andrew P. Morris; Helen M. Colhoun; Mark I. McCarthy; Colin N. A. Palmer

doi:10.1161/CIRCGEN.119.002769

Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus

, CARDIOGRAMplusC4D Steering Committee, Natalie R. Van Zuydam (Lead / Corresponding author), Claes Ladenvall, Benjamin F. Voight, Rona J. Strawbridge, Juan Fernandez-Tajes, N. William Rayner, Neil R. Robertson, Anubha Mahajan, Efthymia Vlachopoulou, Anuj Goel, Marcus E. Kleber, Christopher P. Nelson, Lydia Coulter Kwee, Tõnu Esko, Evelin Mihailov, Reedik Mägi, Lili Milani, Krista FischerStavroula Kanoni, Jitender Kumar, Ci Song, Jaana A. Hartiala, Nancy L. Pedersen, Markus Perola, Christian Gieger, Annette Peters, Liming Qu, Sara M. Willems, Alex S. F. Doney, Andrew D. Morris, Yan Zheng, Giorgio Sesti, Frank B. Hu, Lu Qi, Markku Laakso, Unnur Thorsteinsdottir, Harald Grallert, Cornelia Van Duijn, Muredach P. Reilly, Erik Ingelsson, Panos Deloukas, Sek Kathiresan, Andres Metspalu, Svati H. Shah, Juha Sinisalo, Veikko Salomaa, Andrew P. Morris, Helen M. Colhoun, Mark I. McCarthy, Colin N. A. Palmer

Population Health and Genomics

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Abstract

Background: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).

Methods: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).

Results: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.

Conclusions: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.

Original language	English
Pages (from-to)	640-648
Number of pages	9
Journal	Circulation: Genomic and Precision Medicine
Volume	13
Issue number	6
Early online date	13 Aug 2020
DOIs	https://doi.org/10.1161/CIRCGEN.119.002769
Publication status	Published - Dec 2020

Keywords

blood pressure
coronary artery disease
diabetes mellitus
genome-wide association study
risk factors

ASJC Scopus subject areas

Genetics
Cardiology and Cardiovascular Medicine
Genetics(clinical)

UN SDGs

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

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10.1161/CIRCGEN.119.002769Licence: CC BY

Final Published VersionFinal published version, 1.58 MBLicence: CC BY

Cite this

, CARDIOGRAMplusC4D Steering Committee, Van Zuydam, N. R., Ladenvall, C., Voight, B. F., Strawbridge, R. J., Fernandez-Tajes, J., Rayner, N. W., Robertson, N. R., Mahajan, A., Vlachopoulou, E., Goel, A., Kleber, M. E., Nelson, C. P., Kwee, L. C., Esko, T., Mihailov, E., Mägi, R., Milani, L., ... Palmer, C. N. A. (2020). Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus. Circulation: Genomic and Precision Medicine, 13(6), 640-648. https://doi.org/10.1161/CIRCGEN.119.002769

@article{86d85a7e2f9647709aa9499e8abe8492,

title = "Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus",

abstract = "Background: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).Methods: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).Results: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.Conclusions: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.",

keywords = "blood pressure, coronary artery disease, diabetes mellitus, genome-wide association study, risk factors",

author = "{CARDIOGRAMplusC4D Steering Committee} and {Van Zuydam}, {Natalie R.} and Claes Ladenvall and Voight, {Benjamin F.} and Strawbridge, {Rona J.} and Juan Fernandez-Tajes and Rayner, {N. William} and Robertson, {Neil R.} and Anubha Mahajan and Efthymia Vlachopoulou and Anuj Goel and Kleber, {Marcus E.} and Nelson, {Christopher P.} and Kwee, {Lydia Coulter} and T{\~o}nu Esko and Evelin Mihailov and Reedik M{\"a}gi and Lili Milani and Krista Fischer and Stavroula Kanoni and Jitender Kumar and Ci Song and Hartiala, {Jaana A.} and Pedersen, {Nancy L.} and Markus Perola and Christian Gieger and Annette Peters and Liming Qu and Willems, {Sara M.} and Doney, {Alex S. F.} and Morris, {Andrew D.} and Yan Zheng and Giorgio Sesti and Hu, {Frank B.} and Lu Qi and Markku Laakso and Unnur Thorsteinsdottir and Harald Grallert and {Van Duijn}, Cornelia and Reilly, {Muredach P.} and Erik Ingelsson and Panos Deloukas and Sek Kathiresan and Andres Metspalu and Shah, {Svati H.} and Juha Sinisalo and Veikko Salomaa and Morris, {Andrew P.} and Colhoun, {Helen M.} and McCarthy, {Mark I.} and Palmer, {Colin N. A.}",

note = "This work was supported by the European Union Framework Programme 7 (FP7/2007-2013) for the Innovative Medicine Initiative (IMI) under grant agreement n° IMI/115006 (the SUMMIT [Surrogate Markers for Micro- and Macro-Vascular Hard End Points for Innovative Diabetes Tools] consortium); Aarno Koskelo Foundation; Academy of Finland (no. 263401; no. 2676882); American Heart Association (13SDG14330006); AstraZeneca; AtheroSysMed (Systems medicine of coronary heart disease and stroke); British Heart Foundation Centre of Research Excellence at Oxford; ERC269045-Gene Target T2D grant; Estonian Research Council (IUT20-60, PUT1660 and PUT1665P); Estonian Center of Genomics/Roadmap II (project No. 2014-2020.4.01.16-0125); European Union (no. 692145; no. 633589; no. 313010; LSHM-CT-2007-037273; no. 201668; 2014-2020.4.01.15-0012;QLG1-CT-2002-00896; EU/QLRT-2001-01254; QLG2-CT-2002-01254 HEALTH-F2-2013-601456); Finnish Foundation for Cardiovascular research; Gentransmed - Centre of Excellence for Genomics and Translational Medicine; German Ministry of Education and Research (no. 01ZX1313A-K); Helsinki University Central Hospital special government funds (TYH7215, TKK2012005, TYH2012209, TYH2014312); Juvenile Diabetes Research Foundation (JDRF, 2-SRA-2014-276-Q-R); National Institute of Diabetes and Digestive and Kidney diseases (NIDDK, 5R01DK106236; U01-DK066134; U01-DK105535; R01DK101478); National Heart, Lung and Blood Institute (NLHBI, R01HL103866); National Institute for Health Research (NIHR); Personalized diagnostics and treatment of high risk coronary artery disease patients (RiskyCAD; 305739); Sigrid Juselius Foundation; Finnish Academy (no. 269517); Finnish Foundation for Cardiovascular Research; Foundation for Strategic Research and Stockholm County Council (560283; 592229); Juho Vainio Foundation; Knut and Alice Wallenberg Foundation; Ministry for Higher Education; Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and Stockholm County Council; Swedish Foundation for Strategic Research (SSF; ICA08-0047); Swedish Heart-Lung Foundation; Swedish Research Council (project 8691; 2015-02558; 2016-00598; M-2005-1112 and 2009-2298); Torsten and Ragnar S{\"o}derberg Foundation; W.W. Smith Charitable Trust (H1201); Wellcome Trust Institutional strategic support fund; Yrj{\"o} Jahnsson Foundation",

year = "2020",

month = dec,

doi = "10.1161/CIRCGEN.119.002769",

language = "English",

volume = "13",

pages = "640--648",

journal = "Circulation: Genomic and Precision Medicine",

issn = "2574-8300",

publisher = "Lippincott, Williams & Wilkins",

number = "6",

}

CARDIOGRAMplusC4D Steering Committee, Van Zuydam, NR, Ladenvall, C, Voight, BF, Strawbridge, RJ, Fernandez-Tajes, J, Rayner, NW, Robertson, NR, Mahajan, A, Vlachopoulou, E, Goel, A, Kleber, ME, Nelson, CP, Kwee, LC, Esko, T, Mihailov, E, Mägi, R, Milani, L, Fischer, K, Kanoni, S, Kumar, J, Song, C, Hartiala, JA, Pedersen, NL, Perola, M, Gieger, C, Peters, A, Qu, L, Willems, SM, Doney, ASF, Morris, AD, Zheng, Y, Sesti, G, Hu, FB, Qi, L, Laakso, M, Thorsteinsdottir, U, Grallert, H, Van Duijn, C, Reilly, MP, Ingelsson, E, Deloukas, P, Kathiresan, S, Metspalu, A, Shah, SH, Sinisalo, J, Salomaa, V, Morris, AP, Colhoun, HM & McCarthy, MI & Palmer, CNA 2020, 'Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus', Circulation: Genomic and Precision Medicine, vol. 13, no. 6, pp. 640-648. https://doi.org/10.1161/CIRCGEN.119.002769

TY - JOUR

T1 - Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus

AU - CARDIOGRAMplusC4D Steering Committee

AU - Van Zuydam, Natalie R.

AU - Ladenvall, Claes

AU - Voight, Benjamin F.

AU - Strawbridge, Rona J.

AU - Fernandez-Tajes, Juan

AU - Rayner, N. William

AU - Robertson, Neil R.

AU - Mahajan, Anubha

AU - Vlachopoulou, Efthymia

AU - Goel, Anuj

AU - Kleber, Marcus E.

AU - Nelson, Christopher P.

AU - Kwee, Lydia Coulter

AU - Esko, Tõnu

AU - Mihailov, Evelin

AU - Mägi, Reedik

AU - Milani, Lili

AU - Fischer, Krista

AU - Kanoni, Stavroula

AU - Kumar, Jitender

AU - Song, Ci

AU - Hartiala, Jaana A.

AU - Pedersen, Nancy L.

AU - Perola, Markus

AU - Gieger, Christian

AU - Peters, Annette

AU - Qu, Liming

AU - Willems, Sara M.

AU - Doney, Alex S. F.

AU - Morris, Andrew D.

AU - Zheng, Yan

AU - Sesti, Giorgio

AU - Hu, Frank B.

AU - Qi, Lu

AU - Laakso, Markku

AU - Thorsteinsdottir, Unnur

AU - Grallert, Harald

AU - Van Duijn, Cornelia

AU - Reilly, Muredach P.

AU - Ingelsson, Erik

AU - Deloukas, Panos

AU - Kathiresan, Sek

AU - Metspalu, Andres

AU - Shah, Svati H.

AU - Sinisalo, Juha

AU - Salomaa, Veikko

AU - Morris, Andrew P.

AU - Colhoun, Helen M.

AU - McCarthy, Mark I.

AU - Palmer, Colin N. A.

N1 - This work was supported by the European Union Framework Programme 7 (FP7/2007-2013) for the Innovative Medicine Initiative (IMI) under grant agreement n° IMI/115006 (the SUMMIT [Surrogate Markers for Micro- and Macro-Vascular Hard End Points for Innovative Diabetes Tools] consortium); Aarno Koskelo Foundation; Academy of Finland (no. 263401; no. 2676882); American Heart Association (13SDG14330006); AstraZeneca; AtheroSysMed (Systems medicine of coronary heart disease and stroke); British Heart Foundation Centre of Research Excellence at Oxford; ERC269045-Gene Target T2D grant; Estonian Research Council (IUT20-60, PUT1660 and PUT1665P); Estonian Center of Genomics/Roadmap II (project No. 2014-2020.4.01.16-0125); European Union (no. 692145; no. 633589; no. 313010; LSHM-CT-2007-037273; no. 201668; 2014-2020.4.01.15-0012;QLG1-CT-2002-00896; EU/QLRT-2001-01254; QLG2-CT-2002-01254 HEALTH-F2-2013-601456); Finnish Foundation for Cardiovascular research; Gentransmed - Centre of Excellence for Genomics and Translational Medicine; German Ministry of Education and Research (no. 01ZX1313A-K); Helsinki University Central Hospital special government funds (TYH7215, TKK2012005, TYH2012209, TYH2014312); Juvenile Diabetes Research Foundation (JDRF, 2-SRA-2014-276-Q-R); National Institute of Diabetes and Digestive and Kidney diseases (NIDDK, 5R01DK106236; U01-DK066134; U01-DK105535; R01DK101478); National Heart, Lung and Blood Institute (NLHBI, R01HL103866); National Institute for Health Research (NIHR); Personalized diagnostics and treatment of high risk coronary artery disease patients (RiskyCAD; 305739); Sigrid Juselius Foundation; Finnish Academy (no. 269517); Finnish Foundation for Cardiovascular Research; Foundation for Strategic Research and Stockholm County Council (560283; 592229); Juho Vainio Foundation; Knut and Alice Wallenberg Foundation; Ministry for Higher Education; Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and Stockholm County Council; Swedish Foundation for Strategic Research (SSF; ICA08-0047); Swedish Heart-Lung Foundation; Swedish Research Council (project 8691; 2015-02558; 2016-00598; M-2005-1112 and 2009-2298); Torsten and Ragnar Söderberg Foundation; W.W. Smith Charitable Trust (H1201); Wellcome Trust Institutional strategic support fund; Yrjö Jahnsson Foundation

PY - 2020/12

Y1 - 2020/12

N2 - Background: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).Methods: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).Results: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.Conclusions: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.

AB - Background: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).Methods: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).Results: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.Conclusions: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.

KW - blood pressure

KW - coronary artery disease

KW - diabetes mellitus

KW - genome-wide association study

KW - risk factors

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U2 - 10.1161/CIRCGEN.119.002769

DO - 10.1161/CIRCGEN.119.002769

M3 - Article

C2 - 33321069

AN - SCOPUS:85097959733

SN - 2574-8300

VL - 13

SP - 640

EP - 648

JO - Circulation: Genomic and Precision Medicine

JF - Circulation: Genomic and Precision Medicine

IS - 6

ER -

Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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Palmer, Colin

Cite this

Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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Fingerprint

Profiles

Palmer, Colin

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