Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease

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Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease. / Webb, Thomas R; Erdmann, Jeanette; Stirrups, Kathleen E; Stitziel, Nathan O; Masca, Nicholas G D; Jansen, Henning; Kanoni, Stavroula; Nelson, Christopher P; Ferrario, Paola G; König, Inke R; Eicher, John D; Johnson, Andrew D; Hamby, Stephen E; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric; Auer, Paul L; Björkegren, Johan L M; Weeke, Peter Ejvin; Schick, Ursula M; Lu, Yingchang; Zhang, He; Dubé, Marie-Pierre; Goel, Anuj; Farrall, Martin; Peloso, Gina M; Won, Hong-Hee; Do, Ron; van Iperen, Erik P A; Kruppa, Jochen; Mahajan, Anubha; Scott, Robert A; Willenborg, Christina; Braund, Peter S; van Capelleveen, Julian C; Doney, Alex S F; Donnelly, Louise A; Asselta, Rosanna; Angelica Merlini, Pier; Duga, Stefano; Marziliano, Nicola; Denny, Josh C; Shaffer, Christian M; El Mokhtari, Nour Eddine; Franke, Andre; Heilmann-Heimbach, Stefanie; Hengstenberg, Christian; Hoffmann, Per; Nordestgaard, Børge G; Wellcome Trust Case Control Consortium ; V Varga, Tibor.

I: Journal of the American College of Cardiology, Bind 69, Nr. 7, 21.02.2017, s. 823-836.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Webb, TR, Erdmann, J, Stirrups, KE, Stitziel, NO, Masca, NGD, Jansen, H, Kanoni, S, Nelson, CP, Ferrario, PG, König, IR, Eicher, JD, Johnson, AD, Hamby, SE, Betsholtz, C, Ruusalepp, A, Franzén, O, Schadt, E, Auer, PL, Björkegren, JLM, Weeke, PE, Schick, UM, Lu, Y, Zhang, H, Dubé, M-P, Goel, A, Farrall, M, Peloso, GM, Won, H-H, Do, R, van Iperen, EPA, Kruppa, J, Mahajan, A, Scott, RA, Willenborg, C, Braund, PS, van Capelleveen, JC, Doney, ASF, Donnelly, LA, Asselta, R, Angelica Merlini, P, Duga, S, Marziliano, N, Denny, JC, Shaffer, CM, El Mokhtari, NE, Franke, A, Heilmann-Heimbach, S, Hengstenberg, C, Hoffmann, P, Nordestgaard, BG, Wellcome Trust Case Control Consortium & V Varga, T 2017, 'Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease', Journal of the American College of Cardiology, bind 69, nr. 7, s. 823-836. https://doi.org/10.1016/j.jacc.2016.11.056

APA

Webb, T. R., Erdmann, J., Stirrups, K. E., Stitziel, N. O., Masca, N. G. D., Jansen, H., Kanoni, S., Nelson, C. P., Ferrario, P. G., König, I. R., Eicher, J. D., Johnson, A. D., Hamby, S. E., Betsholtz, C., Ruusalepp, A., Franzén, O., Schadt, E., Auer, P. L., Björkegren, J. L. M., ... V Varga, T. (2017). Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease. Journal of the American College of Cardiology, 69(7), 823-836. https://doi.org/10.1016/j.jacc.2016.11.056

Vancouver

Webb TR, Erdmann J, Stirrups KE, Stitziel NO, Masca NGD, Jansen H o.a. Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease. Journal of the American College of Cardiology. 2017 feb. 21;69(7):823-836. https://doi.org/10.1016/j.jacc.2016.11.056

Author

Webb, Thomas R ; Erdmann, Jeanette ; Stirrups, Kathleen E ; Stitziel, Nathan O ; Masca, Nicholas G D ; Jansen, Henning ; Kanoni, Stavroula ; Nelson, Christopher P ; Ferrario, Paola G ; König, Inke R ; Eicher, John D ; Johnson, Andrew D ; Hamby, Stephen E ; Betsholtz, Christer ; Ruusalepp, Arno ; Franzén, Oscar ; Schadt, Eric ; Auer, Paul L ; Björkegren, Johan L M ; Weeke, Peter Ejvin ; Schick, Ursula M ; Lu, Yingchang ; Zhang, He ; Dubé, Marie-Pierre ; Goel, Anuj ; Farrall, Martin ; Peloso, Gina M ; Won, Hong-Hee ; Do, Ron ; van Iperen, Erik P A ; Kruppa, Jochen ; Mahajan, Anubha ; Scott, Robert A ; Willenborg, Christina ; Braund, Peter S ; van Capelleveen, Julian C ; Doney, Alex S F ; Donnelly, Louise A ; Asselta, Rosanna ; Angelica Merlini, Pier ; Duga, Stefano ; Marziliano, Nicola ; Denny, Josh C ; Shaffer, Christian M ; El Mokhtari, Nour Eddine ; Franke, Andre ; Heilmann-Heimbach, Stefanie ; Hengstenberg, Christian ; Hoffmann, Per ; Nordestgaard, Børge G ; Wellcome Trust Case Control Consortium ; V Varga, Tibor. / Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease. I: Journal of the American College of Cardiology. 2017 ; Bind 69, Nr. 7. s. 823-836.

Bibtex

@article{9d3ae36407594674b4f96dcc11b06d47,

title = "Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease",

abstract = "BACKGROUND: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS: In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS: We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10(-4) with a range of other diseases/traits.CONCLUSIONS: We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.",

keywords = "Journal Article",

author = "Webb, {Thomas R} and Jeanette Erdmann and Stirrups, {Kathleen E} and Stitziel, {Nathan O} and Masca, {Nicholas G D} and Henning Jansen and Stavroula Kanoni and Nelson, {Christopher P} and Ferrario, {Paola G} and K{\"o}nig, {Inke R} and Eicher, {John D} and Johnson, {Andrew D} and Hamby, {Stephen E} and Christer Betsholtz and Arno Ruusalepp and Oscar Franz{\'e}n and Eric Schadt and Auer, {Paul L} and Bj{\"o}rkegren, {Johan L M} and Weeke, {Peter Ejvin} and Schick, {Ursula M} and Yingchang Lu and He Zhang and Marie-Pierre Dub{\'e} and Anuj Goel and Martin Farrall and Peloso, {Gina M} and Hong-Hee Won and Ron Do and {van Iperen}, {Erik P A} and Jochen Kruppa and Anubha Mahajan and Scott, {Robert A} and Christina Willenborg and Braund, {Peter S} and {van Capelleveen}, {Julian C} and Doney, {Alex S F} and Donnelly, {Louise A} and Rosanna Asselta and {Angelica Merlini}, Pier and Stefano Duga and Nicola Marziliano and Denny, {Josh C} and Shaffer, {Christian M} and {El Mokhtari}, {Nour Eddine} and Andre Franke and Stefanie Heilmann-Heimbach and Christian Hengstenberg and Per Hoffmann and Nordestgaard, {B{\o}rge G} and {Wellcome Trust Case Control Consortium} and {V Varga}, Tibor",

year = "2017",

month = feb,

day = "21",

doi = "10.1016/j.jacc.2016.11.056",

language = "English",

volume = "69",

pages = "823--836",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier",

number = "7",

}

RIS

TY - JOUR

T1 - Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease

AU - Webb, Thomas R

AU - Erdmann, Jeanette

AU - Stirrups, Kathleen E

AU - Stitziel, Nathan O

AU - Masca, Nicholas G D

AU - Jansen, Henning

AU - Kanoni, Stavroula

AU - Nelson, Christopher P

AU - Ferrario, Paola G

AU - König, Inke R

AU - Eicher, John D

AU - Johnson, Andrew D

AU - Hamby, Stephen E

AU - Betsholtz, Christer

AU - Ruusalepp, Arno

AU - Franzén, Oscar

AU - Schadt, Eric

AU - Auer, Paul L

AU - Björkegren, Johan L M

AU - Weeke, Peter Ejvin

AU - Schick, Ursula M

AU - Lu, Yingchang

AU - Zhang, He

AU - Dubé, Marie-Pierre

AU - Goel, Anuj

AU - Farrall, Martin

AU - Peloso, Gina M

AU - Won, Hong-Hee

AU - Do, Ron

AU - van Iperen, Erik P A

AU - Kruppa, Jochen

AU - Mahajan, Anubha

AU - Scott, Robert A

AU - Willenborg, Christina

AU - Braund, Peter S

AU - van Capelleveen, Julian C

AU - Doney, Alex S F

AU - Donnelly, Louise A

AU - Asselta, Rosanna

AU - Angelica Merlini, Pier

AU - Duga, Stefano

AU - Marziliano, Nicola

AU - Denny, Josh C

AU - Shaffer, Christian M

AU - El Mokhtari, Nour Eddine

AU - Franke, Andre

AU - Heilmann-Heimbach, Stefanie

AU - Hengstenberg, Christian

AU - Hoffmann, Per

AU - Nordestgaard, Børge G

AU - Wellcome Trust Case Control Consortium

AU - V Varga, Tibor

PY - 2017/2/21

Y1 - 2017/2/21

N2 - BACKGROUND: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS: In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS: We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10(-4) with a range of other diseases/traits.CONCLUSIONS: We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.

AB - BACKGROUND: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS: In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS: We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10(-4) with a range of other diseases/traits.CONCLUSIONS: We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.

KW - Journal Article

U2 - 10.1016/j.jacc.2016.11.056

DO - 10.1016/j.jacc.2016.11.056

M3 - Journal article

C2 - 28209224

VL - 69

SP - 823

EP - 836

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 7

ER -

ID: 179439953