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

doi:10.1016/j.jacc.2016.11.056

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Fältnamn	Indikatorer	Metadata
000		08749naa a22020293a 4500
001		20214750
003		SE-LIBR
005		20170330151409.0
007		cr\|\|\|\|\|\|\|\|\|\|\|\|
008		170330s2017 sw \|\|\|\| o \|\|\|\| \|\|eng c
024	7	a http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3189612 uri
024	7	a urn:nbn:se:uu:diva-3189612 urn
024	7	a 10.1016/j.jacc.2016.11.0562 doi
040		a S
041	0	a eng
042		9 EPLK
100	1	a Webb, Thomas R.4 aut
245	1 0	a Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Diseaseh [Elektronisk resurs]
260		c 2017
500		a Published
506	0	a gratis
520		a 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 x 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.
650	7	a Medical and Health Sciences2 hsv
650	7	a Medicin och hälsovetenskap2 hsv
653	0	a cholesteryl ester transfer protein
653	0	a expression quantitative trait loci
653	0	a genetics
653	0	a genome-wide association
653	0	a single nucleotide polymorphism
700	1	a Erdmann, Jeanette4 aut
700	1	a Stirrups, Kathleen E.4 aut
700	1	a Stitziel, Nathan O.4 aut
700	1	a Masca, Nicholas G. D.4 aut
700	1	a Jansen, Henning4 aut
700	1	a Kanoni, Stavroula4 aut
700	1	a Nelson, Christopher P.4 aut
700	1	a Ferrario, Paola G.4 aut
700	1	a Koenig, Inke R.4 aut
700	1	a Eicher, John D.4 aut
700	1	a Johnson, Andrew D.4 aut
700	1	a Hamby, Stephen E.4 aut
700	1	a Betsholtz, Christer4 aut
700	1	a Ruusalepp, Arno4 aut
700	1	a Franzen, Oscar4 aut
700	1	a Schadt, Eric E.4 aut
700	1	a Bjoerkegren, Johan L. M.4 aut
700	1	a Weeke, Peter E.4 aut
700	1	a Auer, Paul L.4 aut
700	1	a Schick, Ursula M.4 aut
700	1	a Lu, Yingchang4 aut
700	1	a Zhang, He4 aut
700	1	a Dube, Marie-Pierre4 aut
700	1	a Goel, Anuj4 aut
700	1	a Farrall, Martin4 aut
700	1	a Peloso, Gina M.4 aut
700	1	a Won, Hong-Hee4 aut
700	1	a Do, Ron4 aut
700	1	a van Iperen, Erik4 aut
700	1	a Kruppa, Jochen4 aut
700	1	a Mahajan, Anubha4 aut
700	1	a Scott, Robert A.4 aut
700	1	a Willenborg, Christina4 aut
700	1	a Braund, Peter S.4 aut
700	1	a van Capelleveen, Julian C.4 aut
700	1	a Doney, Alex S. F.4 aut
700	1	a Donnelly, Louise A.4 aut
700	1	a Asselta, Rosanna4 aut
700	1	a Merlini, Pier A.4 aut
700	1	a Duga, Stefano4 aut
700	1	a Marziliano, Nicola4 aut
700	1	a Denny, Josh C.4 aut
700	1	a Shaffer, Christian4 aut
700	1	a El-Mokhtari, Nour Eddine4 aut
700	1	a Franke, Andre4 aut
700	1	a Heilmann, Stefanie4 aut
700	1	a Hengstenberg, Christian4 aut
700	1	a Hoffmann, Per4 aut
700	1	a Holmen, Oddgeir L.4 aut
700	1	a Hveem, Kristian4 aut
700	1	a Jansson, Jan-Hakan4 aut
700	1	a Joeckel, Karl-Heinz4 aut
700	1	a Kessler, Thorsten4 aut
700	1	a Kriebel, Jennifer4 aut
700	1	a Laugwitz, Karl L.4 aut
700	1	a Marouli, Eirini4 aut
700	1	a Martinelli, Nicola4 aut
700	1	a McCarthy, Mark I.4 aut
700	1	a Van Zuydam, Natalie R.4 aut
700	1	a Meisinger, Christa4 aut
700	1	a Esko, Tonu4 aut
700	1	a Mihailov, Evelin4 aut
700	1	a Escher, Stefan A.4 aut
700	1	a Alver, Maris4 aut
700	1	a Moebus, Susanne4 aut
700	1	a Morris, Andrew D.4 aut
700	1	a Virtamo, Jarma4 aut
700	1	a Nikpay, Majid4 aut
700	1	a Olivieri, Oliviero4 aut
700	1	a Provost, Sylvie4 aut
700	1	a AlQarawi, Alaa4 aut
700	1	a Robertson, Neil R.4 aut
700	1	a Akinsansya, Karen O.4 aut
700	1	a Reilly, Dermot F.4 aut
700	1	a Vogt, Thomas F.4 aut
700	1	a Yin, Wu4 aut
700	1	a Asselbergs, Folkert W.4 aut
700	1	a Kooperberg, Charles4 aut
700	1	a Jackson, Rebecca D.4 aut
700	1	a Stahl, Eli4 aut
700	1	a Mueller-Nurasyid, Martina4 aut
700	1	a Strauch, Konstantin4 aut
700	1	a Varga, Tibor V.4 aut
700	1	a Waldenberger, Melanie4 aut
700	1	a Zeng, Lingyao4 aut
700	1	a Chowdhury, Rajiv4 aut
700	1	a Salomaa, Veikko4 aut
700	1	a Ford, Ian4 aut
700	1	a Jukema, J. Wouter4 aut
700	1	a Amouyel, Philippe4 aut
700	1	a Kontto, Jukka4 aut
700	1	a Nordestgaard, Borge G.4 aut
700	1	a Ferrieres, Jean4 aut
700	1	a Saleheen, Danish4 aut
700	1	a Sattar, Naveed4 aut
700	1	a Surendran, Praveen4 aut
700	1	a Wagner, Aline4 aut
700	1	a Young, Robin4 aut
700	1	a Howson, Joanna M. M.4 aut
700	1	a Butterworth, Adam S.4 aut
700	1	a Danesh, John4 aut
700	1	a Ardissino, Diego4 aut
700	1	a Bottinger, Erwin P.4 aut
700	1	a Erbel, Raimund4 aut
700	1	a Franks, Paul W.4 aut
700	1	a Girelli, Domenico4 aut
700	1	a Hall, Alistair S.4 aut
700	1	a Hovingh, G. Kees4 aut
700	1	a Kastrati, Adnan4 aut
700	1	a Lieb, Wolfgang4 aut
700	1	a Meitinger, Thomas4 aut
700	1	a Kraus, William E.4 aut
700	1	a Shah, Svati H.4 aut
700	1	a McPherson, Ruth4 aut
700	1	a Orho-Melander, Marju4 aut
700	1	a Melander, Olle4 aut
700	1	a Metspalu, Andres4 aut
700	1	a Palmer, Colin N. A.4 aut
700	1	a Peters, Annette4 aut
700	1	a Rader, Daniel J.4 aut
700	1	a Reilly, Muredach P.4 aut
700	1	a Loos, Ruth J. F.4 aut
700	1	a Reiner, Alex P.4 aut
700	1	a Roden, Dan M.4 aut
700	1	a Tardif, Jean-Claude4 aut
700	1	a Thompson, John R.4 aut
700	1	a Wareham, Nicholas J.4 aut
700	1	a Watkins, Hugh4 aut
700	1	a Willer, Cristen J.4 aut
700	1	a Samani, Nilesh J.4 aut
700	1	a Schunkert, Heribert4 aut
700	1	a Deloukas, Panos4 aut
700	1	a Kathiresan, Sekar4 aut
710	1 2	a Uppsala universitetb Medicinska och farmaceutiska vetenskapsområdet4 pbl
772	1 8	i channel recordw 19753896
773	0 8	i Värdpublikationt Journal of the American College of Cardiologyg 69:7, 823-836x 0735-1097
856	4 0	u http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-318961
856	4 0	u http://dx.doi.org/10.1016/j.jacc.2016.11.056
856	4 0	u http://uu.diva-portal.org/smash/get/diva2:1085599/FULLTEXT01
841		5 APISa x ab 170330\|\|0000\|\|\|\|\|001\|\|\|\|\|\|000000e 1
024	7	5 APISa urn:nbn:se:uu:diva-3189612 urn
852		5 APISb APIS
856	4 0	5 APISu http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-318961

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Av författaren/redakt...: Webb, Thomas R.; Erdmann, Jeanett ...; Stirrups, Kathle ...; Stitziel, Nathan ...; Masca, Nicholas ...; Jansen, Henning; visa fler...; Kanoni, Stavroul ...; Nelson, Christop ...; Ferrario, Paola ...; Koenig, Inke R.; Eicher, John D.; Johnson, Andrew ...; Hamby, Stephen E ...; Betsholtz, Chris ...; Ruusalepp, Arno; Franzen, Oscar; Schadt, Eric E.; Bjoerkegren, Joh ...; Weeke, Peter E.; Auer, Paul L.; Schick, Ursula M ...; Lu, Yingchang; Zhang, He; Dube, Marie-Pier ...; Goel, Anuj; Farrall, Martin; Peloso, Gina M.; Won, Hong-Hee; Do, Ron; van Iperen, Erik; Kruppa, Jochen; Mahajan, Anubha; Scott, Robert A.; Willenborg, Chri ...; Braund, Peter S.; van Capelleveen, ...; Doney, Alex S. F ...; Donnelly, Louise ...; Asselta, Rosanna; Merlini, Pier A.; Duga, Stefano; Marziliano, Nico ...; Denny, Josh C.; Shaffer, Christi ...; El-Mokhtari, Nou ...; Franke, Andre; Heilmann, Stefan ...; Hengstenberg, Ch ...; Hoffmann, Per; Holmen, Oddgeir ...; Hveem, Kristian; Jansson, Jan-Hak ...; Joeckel, Karl-He ...; Kessler, Thorste ...; Kriebel, Jennife ...; Laugwitz, Karl L ...; Marouli, Eirini; Martinelli, Nico ...; McCarthy, Mark I ...; Van Zuydam, Nata ...; Meisinger, Chris ...; Esko, Tonu; Mihailov, Evelin; Escher, Stefan A ...; Alver, Maris; Moebus, Susanne; Morris, Andrew D ...; Virtamo, Jarma; Nikpay, Majid; Olivieri, Olivie ...; Provost, Sylvie; AlQarawi, Alaa; Robertson, Neil ...; Akinsansya, Kare ...; Reilly, Dermot F ...; Vogt, Thomas F.; Yin, Wu; Asselbergs, Folk ...; Kooperberg, Char ...; Jackson, Rebecca ...; Stahl, Eli; Mueller-Nurasyid ...; Strauch, Konstan ...; Varga, Tibor V.; Waldenberger, Me ...; Zeng, Lingyao; Chowdhury, Rajiv; Salomaa, Veikko; Ford, Ian; Jukema, J. Woute ...; Amouyel, Philipp ...; Kontto, Jukka; Nordestgaard, Bo ...; Ferrieres, Jean; Saleheen, Danish; Sattar, Naveed; Surendran, Prave ...; Wagner, Aline; Young, Robin; Howson, Joanna M ...; Butterworth, Ada ...; Danesh, John; Ardissino, Diego; Bottinger, Erwin ...; Erbel, Raimund; Franks, Paul W.; Girelli, Domenic ...; Hall, Alistair S ...; Hovingh, G. Kees; Kastrati, Adnan; Lieb, Wolfgang; Meitinger, Thoma ...; Kraus, William E ...; Shah, Svati H.; McPherson, Ruth; Orho-Melander, M ...; Melander, Olle; Metspalu, Andres; Palmer, Colin N. ...; Peters, Annette; Rader, Daniel J.; Reilly, Muredach ...; Loos, Ruth J. F.; Reiner, Alex P.; Roden, Dan M.; Tardif, Jean-Cla ...; Thompson, John R ...; Wareham, Nichola ...; Watkins, Hugh; Willer, Cristen ...; Samani, Nilesh J ...; Schunkert, Herib ...; Deloukas, Panos; Kathiresan, Seka ...; visa färre...

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