Large-scale association analysis identifies new risk loci for coronary artery disease

Panos Deloukas; Stavroula Kanoni; Christina Willenborg; Martin Farrall; Themistocles L Assimes; John R Thompson; Erik Ingelsson; Danish Saleheen; Jeanette Erdmann; Benjamin A Goldstein; Kathleen Stirrups; Inke R König; Jean-Baptiste Cazier; Asa Johansson; Alistair S Hall; Jong-Young Lee; Cristen J Willer; John C Chambers; Tõnu Esko; Lasse Folkersen; Anuj Goel; Elin Grundberg; Aki S Havulinna; Weang K Ho; Jemma C Hopewell; Niclas Eriksson; Marcus E Kleber; Kati Kristiansson; Per Lundmark; Leo-Pekka Lyytikäinen; Suzanne Rafelt; Dmitry Shungin; Rona J Strawbridge; Gudmar Thorleifsson; Emmi Tikkanen; Natalie Van Zuydam; Benjamin F Voight; Lindsay L Waite; Weihua Zhang; Andreas Ziegler; Devin Absher; David Altshuler; Anthony J Balmforth; Inês Barroso; Peter S Braund; Christof Burgdorf; Simone Claudi-Boehm; David Cox; Maria Dimitriou; Joshua W Knowles; CARDIoGRAM+C4D Consortium

doi:10.1038/ng.2480

Large-scale association analysis identifies new risk loci for coronary artery disease

Panos Deloukas, Stavroula Kanoni, Christina Willenborg, Martin Farrall, Themistocles L Assimes, John R Thompson, Erik Ingelsson, Danish Saleheen, Jeanette Erdmann, Benjamin A Goldstein, Kathleen Stirrups, Inke R König, Jean-Baptiste Cazier, Asa Johansson, Alistair S Hall, Jong-Young Lee, Cristen J Willer, John C Chambers, Tõnu Esko, Lasse FolkersenAnuj Goel, Elin Grundberg, Aki S Havulinna, Weang K Ho, Jemma C Hopewell, Niclas Eriksson, Marcus E Kleber, Kati Kristiansson, Per Lundmark, Leo-Pekka Lyytikäinen, Suzanne Rafelt, Dmitry Shungin, Rona J Strawbridge, Gudmar Thorleifsson, Emmi Tikkanen, Natalie Van Zuydam, Benjamin F Voight, Lindsay L Waite, Weihua Zhang, Andreas Ziegler, Devin Absher, David Altshuler, Anthony J Balmforth, Inês Barroso, Peter S Braund, Christof Burgdorf, Simone Claudi-Boehm, David Cox, Maria Dimitriou, Joshua W Knowles, CARDIoGRAM+C4D Consortium

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Abstract

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

Original language	English
Pages (from-to)	25-33
Number of pages	9
Journal	Nature Genetics
Volume	45
Issue number	1
DOIs	https://doi.org/10.1038/ng.2480
Publication status	Published - Jan 2013

Keywords

Adult
Aged
Asian Continental Ancestry Group
Cell Line
Coronary Artery Disease
European Continental Ancestry Group
Female
Gene Regulatory Networks
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Risk Factors

UN SDGs

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

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10.1038/ng.2480

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Deloukas, P., Kanoni, S., Willenborg, C., Farrall, M., Assimes, T. L., Thompson, J. R., Ingelsson, E., Saleheen, D., Erdmann, J., Goldstein, B. A., Stirrups, K., König, I. R., Cazier, J-B., Johansson, A., Hall, A. S., Lee, J-Y., Willer, C. J., Chambers, J. C., Esko, T., ... CARDIoGRAM+C4D Consortium (2013). Large-scale association analysis identifies new risk loci for coronary artery disease. Nature Genetics, 45(1), 25-33. https://doi.org/10.1038/ng.2480

@article{d5530741644c43c88f664d1850e8791c,

title = "Large-scale association analysis identifies new risk loci for coronary artery disease",

abstract = "Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.",

keywords = "Adult, Aged, Asian Continental Ancestry Group, Cell Line, Coronary Artery Disease, European Continental Ancestry Group, Female, Gene Regulatory Networks, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors",

author = "Panos Deloukas and Stavroula Kanoni and Christina Willenborg and Martin Farrall and Assimes, {Themistocles L} and Thompson, {John R} and Erik Ingelsson and Danish Saleheen and Jeanette Erdmann and Goldstein, {Benjamin A} and Kathleen Stirrups and K{\"o}nig, {Inke R} and Jean-Baptiste Cazier and Asa Johansson and Hall, {Alistair S} and Jong-Young Lee and Willer, {Cristen J} and Chambers, {John C} and T{\~o}nu Esko and Lasse Folkersen and Anuj Goel and Elin Grundberg and Havulinna, {Aki S} and Ho, {Weang K} and Hopewell, {Jemma C} and Niclas Eriksson and Kleber, {Marcus E} and Kati Kristiansson and Per Lundmark and Leo-Pekka Lyytik{\"a}inen and Suzanne Rafelt and Dmitry Shungin and Strawbridge, {Rona J} and Gudmar Thorleifsson and Emmi Tikkanen and {Van Zuydam}, Natalie and Voight, {Benjamin F} and Waite, {Lindsay L} and Weihua Zhang and Andreas Ziegler and Devin Absher and David Altshuler and Balmforth, {Anthony J} and In{\^e}s Barroso and Braund, {Peter S} and Christof Burgdorf and Simone Claudi-Boehm and David Cox and Maria Dimitriou and Knowles, {Joshua W} and {CARDIoGRAM+C4D Consortium}",

year = "2013",

month = jan,

doi = "10.1038/ng.2480",

language = "English",

volume = "45",

pages = "25--33",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "1",

}

Deloukas, P, Kanoni, S, Willenborg, C, Farrall, M, Assimes, TL, Thompson, JR, Ingelsson, E, Saleheen, D, Erdmann, J, Goldstein, BA, Stirrups, K, König, IR, Cazier, J-B, Johansson, A, Hall, AS, Lee, J-Y, Willer, CJ, Chambers, JC, Esko, T, Folkersen, L, Goel, A, Grundberg, E, Havulinna, AS, Ho, WK, Hopewell, JC, Eriksson, N, Kleber, ME, Kristiansson, K, Lundmark, P, Lyytikäinen, L-P, Rafelt, S, Shungin, D, Strawbridge, RJ, Thorleifsson, G, Tikkanen, E, Van Zuydam, N, Voight, BF, Waite, LL, Zhang, W, Ziegler, A, Absher, D, Altshuler, D, Balmforth, AJ, Barroso, I, Braund, PS, Burgdorf, C, Claudi-Boehm, S, Cox, D, Dimitriou, M, Knowles, JW & CARDIoGRAM+C4D Consortium 2013, 'Large-scale association analysis identifies new risk loci for coronary artery disease', Nature Genetics, vol. 45, no. 1, pp. 25-33. https://doi.org/10.1038/ng.2480

TY - JOUR

T1 - Large-scale association analysis identifies new risk loci for coronary artery disease

AU - Deloukas, Panos

AU - Kanoni, Stavroula

AU - Willenborg, Christina

AU - Farrall, Martin

AU - Assimes, Themistocles L

AU - Thompson, John R

AU - Ingelsson, Erik

AU - Saleheen, Danish

AU - Erdmann, Jeanette

AU - Goldstein, Benjamin A

AU - Stirrups, Kathleen

AU - König, Inke R

AU - Cazier, Jean-Baptiste

AU - Johansson, Asa

AU - Hall, Alistair S

AU - Lee, Jong-Young

AU - Willer, Cristen J

AU - Chambers, John C

AU - Esko, Tõnu

AU - Folkersen, Lasse

AU - Goel, Anuj

AU - Grundberg, Elin

AU - Havulinna, Aki S

AU - Ho, Weang K

AU - Hopewell, Jemma C

AU - Eriksson, Niclas

AU - Kleber, Marcus E

AU - Kristiansson, Kati

AU - Lundmark, Per

AU - Lyytikäinen, Leo-Pekka

AU - Rafelt, Suzanne

AU - Shungin, Dmitry

AU - Strawbridge, Rona J

AU - Thorleifsson, Gudmar

AU - Tikkanen, Emmi

AU - Van Zuydam, Natalie

AU - Voight, Benjamin F

AU - Waite, Lindsay L

AU - Zhang, Weihua

AU - Ziegler, Andreas

AU - Absher, Devin

AU - Altshuler, David

AU - Balmforth, Anthony J

AU - Barroso, Inês

AU - Braund, Peter S

AU - Burgdorf, Christof

AU - Claudi-Boehm, Simone

AU - Cox, David

AU - Dimitriou, Maria

AU - Knowles, Joshua W

AU - CARDIoGRAM+C4D Consortium

PY - 2013/1

Y1 - 2013/1

N2 - Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

AB - Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

KW - Adult

KW - Aged

KW - Asian Continental Ancestry Group

KW - Cell Line

KW - Coronary Artery Disease

KW - European Continental Ancestry Group

KW - Female

KW - Gene Regulatory Networks

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

KW - Risk Factors

U2 - 10.1038/ng.2480

DO - 10.1038/ng.2480

M3 - Article

C2 - 23202125

SN - 1061-4036

VL - 45

SP - 25

EP - 33

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

Large-scale association analysis identifies new risk loci for coronary artery disease

Abstract

Keywords

UN SDGs

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