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 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; 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; SUMMIT Steering Committee; CARDIOGRAMplusC4D Steering Committee*

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 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
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
SUMMIT Steering Committee; CARDIOGRAMplusC4D Steering Committee*

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.

Bibliographical data

Original language	English
Article number	e002769
ISSN	2574-8300
DOIs	https://doi.org/10.1161/CIRCGEN.119.002769
Publication status	Published - 12.2020
Externally published	Yes

PubMed	33321069