Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus

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 P. 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; Anders Hamsten; Nilesh J. Samani; Winfried März; Stanley L. Hazen; Hugh Watkins; Danish Saleheen; Andrew P. Morris; Helen M. Colhoun; Leif Groop; Mark I. Mccarthy; Colin N.a. Palmer; John Danesh; Jeanette Erdmann; Dongfeng Gu; Jaspal S. Kooner; Robert Roberts; Heribert Schunkert; Themistocles L. Assimes; Stefan Blankenberg; Bernhard O. Boehm; John C. Chambers; Robert Clarke; Rory Collins; George Dedoussis; Paul W. Franks; G. Kees Hovingh; Bong-jo Kim; Terho Lehtimäki; Ruth Mcpherson; Markku S Nieminen; Christopher O’donnell; Samuli Ripatti; Manjinder S Sandhu; Stefan Schreiber; Agneta Siegbahn; Cristen J. Willer; Pierre A. Zalloua; Michael Mark; Timo Kanninen; Barbara Thorand; Giuseppe Remuzzi; David Dunger; Angela Shore; Ulf Smith; Per-henrik Groop; Seppo Ylä-herttuala; Claudio Cobelli; Riccardo Bellazzi; Ele Ferrannini; Carlo Patrono; Pirjo Nuutila; Paul Mckeague; Birgit Steckel-hamann; Li-ming Gan; Everson Nogoceke; Piero Tortoli; Bernd Jablonka; Mary-julia Brosnan

doi:10.1161/CIRCGEN.119.002769

Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus

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 KumarCi Song, Jaana A. Hartiala, Nancy L. Pedersen, Markus Perola, Christian Gieger, Annette Peters, Liming Qu, Sara M. Willems, Alex S.f. Doney, Andrew P. 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, Anders Hamsten, Nilesh J. Samani, Winfried März, Stanley L. Hazen, Hugh Watkins, Danish Saleheen, Andrew P. Morris, Helen M. Colhoun, Leif Groop, Mark I. Mccarthy, Colin N.a. Palmer, John Danesh, Jeanette Erdmann, Dongfeng Gu, Jaspal S. Kooner, Robert Roberts, Heribert Schunkert, Themistocles L. Assimes, Stefan Blankenberg, Bernhard O. Boehm, John C. Chambers, Robert Clarke, Rory Collins, George Dedoussis, Paul W. Franks, G. Kees Hovingh, Bong-jo Kim, Terho Lehtimäki, Ruth Mcpherson, Markku S Nieminen, Christopher O’donnell, Samuli Ripatti, Manjinder S Sandhu, Stefan Schreiber, Agneta Siegbahn, Cristen J. Willer, Pierre A. Zalloua, Michael Mark, Timo Kanninen, Barbara Thorand, Giuseppe Remuzzi, David Dunger, Angela Shore, Ulf Smith, Per-henrik Groop, Seppo Ylä-herttuala, Claudio Cobelli, Riccardo Bellazzi, Ele Ferrannini, Carlo Patrono, Pirjo Nuutila, Paul Mckeague, Birgit Steckel-hamann, Li-ming Gan, Everson Nogoceke, Piero Tortoli, Bernd Jablonka, Mary-julia Brosnan

Division of Musculoskeletal & Dermatological Sciences (L5)

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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
Journal	Circulation: Genomic and precision medicine
Volume	13
Issue number	6
DOIs	https://doi.org/10.1161/CIRCGEN.119.002769
Publication status	Published - 13 Aug 2020

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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., Fischer, K., Kanoni, S., ... Brosnan, M. (2020). Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus. Circulation: Genomic and precision medicine, 13(6). https://doi.org/10.1161/CIRCGEN.119.002769

@article{9459964555c04f11be9dac73a477e47a,

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.",

author = "\{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 P.\} 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 Anders Hamsten and Samani, \{Nilesh J.\} and Winfried M{\"a}rz and Hazen, \{Stanley L.\} and Hugh Watkins and Danish Saleheen and Morris, \{Andrew P.\} and Colhoun, \{Helen M.\} and Leif Groop and Mccarthy, \{Mark I.\} and Palmer, \{Colin N.a.\} and John Danesh and Jeanette Erdmann and Dongfeng Gu and Kooner, \{Jaspal S.\} and Robert Roberts and Heribert Schunkert and Assimes, \{Themistocles L.\} and Stefan Blankenberg and Boehm, \{Bernhard O.\} and Chambers, \{John C.\} and Robert Clarke and Rory Collins and George Dedoussis and Franks, \{Paul W.\} and Hovingh, \{G. Kees\} and Bong-jo Kim and Terho Lehtim{\"a}ki and Ruth Mcpherson and Nieminen, \{Markku S\} and Christopher O{\textquoteright}donnell and Samuli Ripatti and Sandhu, \{Manjinder S\} and Stefan Schreiber and Agneta Siegbahn and Willer, \{Cristen J.\} and Zalloua, \{Pierre A.\} and Michael Mark and Timo Kanninen and Barbara Thorand and Giuseppe Remuzzi and David Dunger and Angela Shore and Ulf Smith and Per-henrik Groop and Seppo Yl{\"a}-herttuala and Claudio Cobelli and Riccardo Bellazzi and Ele Ferrannini and Carlo Patrono and Pirjo Nuutila and Paul Mckeague and Birgit Steckel-hamann and Li-ming Gan and Everson Nogoceke and Piero Tortoli and Bernd Jablonka and Mary-julia Brosnan",

year = "2020",

month = aug,

day = "13",

doi = "10.1161/CIRCGEN.119.002769",

language = "English",

volume = "13",

journal = "Circulation: Genomic and precision medicine",

issn = "2574-8300",

publisher = "Lippincott Williams \& Wilkins",

number = "6",

}

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, AP, 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, Hamsten, A, Samani, NJ, März, W, Hazen, SL, Watkins, H, Saleheen, D, Morris, AP, Colhoun, HM, Groop, L, Mccarthy, MI, Palmer, CNA, Danesh, J, Erdmann, J, Gu, D, Kooner, JS, Roberts, R, Schunkert, H, Assimes, TL, Blankenberg, S, Boehm, BO, Chambers, JC, Clarke, R, Collins, R, Dedoussis, G, Franks, PW, Hovingh, GK, Kim, B, Lehtimäki, T, Mcpherson, R, Nieminen, MS, O’donnell, C, Ripatti, S, Sandhu, MS, Schreiber, S, Siegbahn, A, Willer, CJ, Zalloua, PA, Mark, M, Kanninen, T, Thorand, B, Remuzzi, G, Dunger, D, Shore, A, Smith, U, Groop, P, Ylä-herttuala, S, Cobelli, C, Bellazzi, R, Ferrannini, E, Patrono, C, Nuutila, P, Mckeague, P, Steckel-hamann, B, Gan, L, Nogoceke, E, Tortoli, P, Jablonka, B & Brosnan, M 2020, 'Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus', Circulation: Genomic and precision medicine, vol. 13, no. 6. https://doi.org/10.1161/CIRCGEN.119.002769

TY - JOUR

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

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 P.

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 - Hamsten, Anders

AU - Samani, Nilesh J.

AU - März, Winfried

AU - Hazen, Stanley L.

AU - Watkins, Hugh

AU - Saleheen, Danish

AU - Morris, Andrew P.

AU - Colhoun, Helen M.

AU - Groop, Leif

AU - Mccarthy, Mark I.

AU - Palmer, Colin N.a.

AU - Danesh, John

AU - Erdmann, Jeanette

AU - Gu, Dongfeng

AU - Kooner, Jaspal S.

AU - Roberts, Robert

AU - Schunkert, Heribert

AU - Assimes, Themistocles L.

AU - Blankenberg, Stefan

AU - Boehm, Bernhard O.

AU - Chambers, John C.

AU - Clarke, Robert

AU - Collins, Rory

AU - Dedoussis, George

AU - Franks, Paul W.

AU - Hovingh, G. Kees

AU - Kim, Bong-jo

AU - Lehtimäki, Terho

AU - Mcpherson, Ruth

AU - Nieminen, Markku S

AU - O’donnell, Christopher

AU - Ripatti, Samuli

AU - Sandhu, Manjinder S

AU - Schreiber, Stefan

AU - Siegbahn, Agneta

AU - Willer, Cristen J.

AU - Zalloua, Pierre A.

AU - Mark, Michael

AU - Kanninen, Timo

AU - Thorand, Barbara

AU - Remuzzi, Giuseppe

AU - Dunger, David

AU - Shore, Angela

AU - Smith, Ulf

AU - Groop, Per-henrik

AU - Ylä-herttuala, Seppo

AU - Cobelli, Claudio

AU - Bellazzi, Riccardo

AU - Ferrannini, Ele

AU - Patrono, Carlo

AU - Nuutila, Pirjo

AU - Mckeague, Paul

AU - Steckel-hamann, Birgit

AU - Gan, Li-ming

AU - Nogoceke, Everson

AU - Tortoli, Piero

AU - Jablonka, Bernd

AU - Brosnan, Mary-julia

PY - 2020/8/13

Y1 - 2020/8/13

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.

UR - https://www.scopus.com/pages/publications/85097959733

U2 - 10.1161/CIRCGEN.119.002769

DO - 10.1161/CIRCGEN.119.002769

M3 - Article

SN - 2574-8300

VL - 13

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

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