Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function
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Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function. / Wild, Philipp S; Felix, Janine F; Schillert, Arne; Teumer, Alexander; Chen, Ming-Huei; Leening, Maarten J G; Völker, Uwe; Großmann, Vera; Brody, Jennifer A; Irvin, Marguerite R; Shah, Sanjiv J; Pramana, Setia; Lieb, Wolfgang; Schmidt, Reinhold; Stanton, Alice V; Malzahn, Dörthe; Smith, Albert Vernon; Sundström, Johan; Minelli, Cosetta; Ruggiero, Daniela; Lyytikäinen, Leo-Pekka; Tiller, Daniel; Smith, J Gustav; Monnereau, Claire; Di Tullio, Marco R; Musani, Solomon K; Morrison, Alanna C; Pers, Tune H; Morley, Michael; Kleber, Marcus E; Aragam, Jayashri; Benjamin, Emelia J; Bis, Joshua C; Bisping, Egbert; Broeckel, Ulrich; Cheng, Susan; Deckers, Jaap W; Del Greco M, Fabiola; Edelmann, Frank; Fornage, Myriam; Franke, Lude; Friedrich, Nele; Harris, Tamara B; Hofer, Edith; Hofman, Albert; Huang, Jie; Hughes, Alun D; Kähönen, Mika; Investigators, Knhi; Kruppa, Jochen; Lackner, Karl J; Lannfelt, Lars; Laskowski, Rafael; Launer, Lenore J; Leosdottir, Margrét; Lin, Honghuang; Lindgren, Cecilia M; Loley, Christina; MacRae, Calum A; Mascalzoni, Deborah; Mayet, Jamil; Medenwald, Daniel; Morris, Andrew P; Müller, Christian; Müller-Nurasyid, Martina; Nappo, Stefania; Nilsson, Peter M; Nuding, Sebastian; Nutile, Teresa; Peters, Annette; Pfeufer, Arne; Pietzner, Diana; Pramstaller, Peter P; Raitakari, Olli T; Rice, Kenneth M; Rivadeneira, Fernando; Rotter, Jerome I; Ruohonen, Saku T; Sacco, Ralph L; Samdarshi, Tandaw E; Schmidt, Helena; Sharp, Andrew S P; Shields, Denis C; Sorice, Rossella; Sotoodehnia, Nona; Stricker, Bruno H; Surendran, Praveen; Thom, Simon; Töglhofer, Anna M; Uitterlinden, André G; Wachter, Rolf; Völzke, Henry; Ziegler, Andreas; Münzel, Thomas; März, Winfried; Cappola, Thomas P; Hirschhorn, Joel N; Mitchell, Gary F; Smith, Nicholas L; Fox, Ervin R; Dueker, Nicole D; Jaddoe, Vincent W V; Melander, Olle; Russ, Martin; Lehtimäki, Terho; Ciullo, Marina; Hicks, Andrew A; Lind, Lars; Gudnason, Vilmundur; Pieske, Burkert; Barron, Anthony J; Zweiker, Robert; Schunkert, Heribert; Ingelsson, Erik; Liu, Kiang; Arnett, Donna K; Psaty, Bruce M; Blankenberg, Stefan; Larson, Martin G; Felix, Stephan B; Franco, Oscar H; Zeller, Tanja; Vasan, Ramachandran S; Dörr, Marcus.
in: J CLIN INVEST, Jahrgang 127, Nr. 5, 01.05.2017, S. 1798-1812.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function
AU - Wild, Philipp S
AU - Felix, Janine F
AU - Schillert, Arne
AU - Teumer, Alexander
AU - Chen, Ming-Huei
AU - Leening, Maarten J G
AU - Völker, Uwe
AU - Großmann, Vera
AU - Brody, Jennifer A
AU - Irvin, Marguerite R
AU - Shah, Sanjiv J
AU - Pramana, Setia
AU - Lieb, Wolfgang
AU - Schmidt, Reinhold
AU - Stanton, Alice V
AU - Malzahn, Dörthe
AU - Smith, Albert Vernon
AU - Sundström, Johan
AU - Minelli, Cosetta
AU - Ruggiero, Daniela
AU - Lyytikäinen, Leo-Pekka
AU - Tiller, Daniel
AU - Smith, J Gustav
AU - Monnereau, Claire
AU - Di Tullio, Marco R
AU - Musani, Solomon K
AU - Morrison, Alanna C
AU - Pers, Tune H
AU - Morley, Michael
AU - Kleber, Marcus E
AU - Aragam, Jayashri
AU - Benjamin, Emelia J
AU - Bis, Joshua C
AU - Bisping, Egbert
AU - Broeckel, Ulrich
AU - Cheng, Susan
AU - Deckers, Jaap W
AU - Del Greco M, Fabiola
AU - Edelmann, Frank
AU - Fornage, Myriam
AU - Franke, Lude
AU - Friedrich, Nele
AU - Harris, Tamara B
AU - Hofer, Edith
AU - Hofman, Albert
AU - Huang, Jie
AU - Hughes, Alun D
AU - Kähönen, Mika
AU - Investigators, Knhi
AU - Kruppa, Jochen
AU - Lackner, Karl J
AU - Lannfelt, Lars
AU - Laskowski, Rafael
AU - Launer, Lenore J
AU - Leosdottir, Margrét
AU - Lin, Honghuang
AU - Lindgren, Cecilia M
AU - Loley, Christina
AU - MacRae, Calum A
AU - Mascalzoni, Deborah
AU - Mayet, Jamil
AU - Medenwald, Daniel
AU - Morris, Andrew P
AU - Müller, Christian
AU - Müller-Nurasyid, Martina
AU - Nappo, Stefania
AU - Nilsson, Peter M
AU - Nuding, Sebastian
AU - Nutile, Teresa
AU - Peters, Annette
AU - Pfeufer, Arne
AU - Pietzner, Diana
AU - Pramstaller, Peter P
AU - Raitakari, Olli T
AU - Rice, Kenneth M
AU - Rivadeneira, Fernando
AU - Rotter, Jerome I
AU - Ruohonen, Saku T
AU - Sacco, Ralph L
AU - Samdarshi, Tandaw E
AU - Schmidt, Helena
AU - Sharp, Andrew S P
AU - Shields, Denis C
AU - Sorice, Rossella
AU - Sotoodehnia, Nona
AU - Stricker, Bruno H
AU - Surendran, Praveen
AU - Thom, Simon
AU - Töglhofer, Anna M
AU - Uitterlinden, André G
AU - Wachter, Rolf
AU - Völzke, Henry
AU - Ziegler, Andreas
AU - Münzel, Thomas
AU - März, Winfried
AU - Cappola, Thomas P
AU - Hirschhorn, Joel N
AU - Mitchell, Gary F
AU - Smith, Nicholas L
AU - Fox, Ervin R
AU - Dueker, Nicole D
AU - Jaddoe, Vincent W V
AU - Melander, Olle
AU - Russ, Martin
AU - Lehtimäki, Terho
AU - Ciullo, Marina
AU - Hicks, Andrew A
AU - Lind, Lars
AU - Gudnason, Vilmundur
AU - Pieske, Burkert
AU - Barron, Anthony J
AU - Zweiker, Robert
AU - Schunkert, Heribert
AU - Ingelsson, Erik
AU - Liu, Kiang
AU - Arnett, Donna K
AU - Psaty, Bruce M
AU - Blankenberg, Stefan
AU - Larson, Martin G
AU - Felix, Stephan B
AU - Franco, Oscar H
AU - Zeller, Tanja
AU - Vasan, Ramachandran S
AU - Dörr, Marcus
PY - 2017/5/1
Y1 - 2017/5/1
N2 - BACKGROUND: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function.METHODS: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function.RESULTS: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue.CONCLUSION: The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies.FUNDING: For detailed information per study, see Acknowledgments.
AB - BACKGROUND: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function.METHODS: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function.RESULTS: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue.CONCLUSION: The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies.FUNDING: For detailed information per study, see Acknowledgments.
KW - Female
KW - Genetic Loci
KW - Genome-Wide Association Study
KW - Heart Diseases/genetics
KW - Humans
KW - Male
KW - Myocardium
KW - Polymorphism, Single Nucleotide
KW - Quantitative Trait, Heritable
U2 - 10.1172/JCI84840
DO - 10.1172/JCI84840
M3 - SCORING: Journal article
C2 - 28394258
VL - 127
SP - 1798
EP - 1812
JO - J CLIN INVEST
JF - J CLIN INVEST
SN - 0021-9738
IS - 5
ER -