TY - JOUR
T1 - Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function.
JF - J Clin Invest
Y1 - 2017
A1 - Wild, Philipp S
A1 - Felix, Janine F
A1 - Schillert, Arne
A1 - Teumer, Alexander
A1 - Chen, Ming-Huei
A1 - Leening, Maarten J G
A1 - Völker, Uwe
A1 - Großmann, Vera
A1 - Brody, Jennifer A
A1 - Irvin, Marguerite R
A1 - Shah, Sanjiv J
A1 - Pramana, Setia
A1 - Lieb, Wolfgang
A1 - Schmidt, Reinhold
A1 - Stanton, Alice V
A1 - Malzahn, Dörthe
A1 - Smith, Albert Vernon
A1 - Sundström, Johan
A1 - Minelli, Cosetta
A1 - Ruggiero, Daniela
A1 - Lyytikäinen, Leo-Pekka
A1 - Tiller, Daniel
A1 - Smith, J Gustav
A1 - Monnereau, Claire
A1 - Di Tullio, Marco R
A1 - Musani, Solomon K
A1 - Morrison, Alanna C
A1 - Pers, Tune H
A1 - Morley, Michael
A1 - Kleber, Marcus E
A1 - Aragam, Jayashri
A1 - Benjamin, Emelia J
A1 - Bis, Joshua C
A1 - Bisping, Egbert
A1 - Broeckel, Ulrich
A1 - Cheng, Susan
A1 - Deckers, Jaap W
A1 - del Greco M, Fabiola
A1 - Edelmann, Frank
A1 - Fornage, Myriam
A1 - Franke, Lude
A1 - Friedrich, Nele
A1 - Harris, Tamara B
A1 - Hofer, Edith
A1 - Hofman, Albert
A1 - Huang, Jie
A1 - Hughes, Alun D
A1 - Kähönen, Mika
A1 - Investigators, Knhi
A1 - Kruppa, Jochen
A1 - Lackner, Karl J
A1 - Lannfelt, Lars
A1 - Laskowski, Rafael
A1 - Launer, Lenore J
A1 - Leosdottir, Margrét
A1 - Lin, Honghuang
A1 - Lindgren, Cecilia M
A1 - Loley, Christina
A1 - MacRae, Calum A
A1 - Mascalzoni, Deborah
A1 - Mayet, Jamil
A1 - Medenwald, Daniel
A1 - Morris, Andrew P
A1 - Müller, Christian
A1 - Müller-Nurasyid, Martina
A1 - Nappo, Stefania
A1 - Nilsson, Peter M
A1 - Nuding, Sebastian
A1 - Nutile, Teresa
A1 - Peters, Annette
A1 - Pfeufer, Arne
A1 - Pietzner, Diana
A1 - Pramstaller, Peter P
A1 - Raitakari, Olli T
A1 - Rice, Kenneth M
A1 - Rivadeneira, Fernando
A1 - Rotter, Jerome I
A1 - Ruohonen, Saku T
A1 - Sacco, Ralph L
A1 - Samdarshi, Tandaw E
A1 - Schmidt, Helena
A1 - Sharp, Andrew S P
A1 - Shields, Denis C
A1 - Sorice, Rossella
A1 - Sotoodehnia, Nona
A1 - Stricker, Bruno H
A1 - Surendran, Praveen
A1 - Thom, Simon
A1 - Töglhofer, Anna M
A1 - Uitterlinden, André G
A1 - Wachter, Rolf
A1 - Völzke, Henry
A1 - Ziegler, Andreas
A1 - Münzel, Thomas
A1 - März, Winfried
A1 - Cappola, Thomas P
A1 - Hirschhorn, Joel N
A1 - Mitchell, Gary F
A1 - Smith, Nicholas L
A1 - Fox, Ervin R
A1 - Dueker, Nicole D
A1 - Jaddoe, Vincent W V
A1 - Melander, Olle
A1 - Russ, Martin
A1 - Lehtimäki, Terho
A1 - Ciullo, Marina
A1 - Hicks, Andrew A
A1 - Lind, Lars
A1 - Gudnason, Vilmundur
A1 - Pieske, Burkert
A1 - Barron, Anthony J
A1 - Zweiker, Robert
A1 - Schunkert, Heribert
A1 - Ingelsson, Erik
A1 - Liu, Kiang
A1 - Arnett, Donna K
A1 - Psaty, Bruce M
A1 - Blankenberg, Stefan
A1 - Larson, Martin G
A1 - Felix, Stephan B
A1 - Franco, Oscar H
A1 - Zeller, Tanja
A1 - Vasan, Ramachandran S
A1 - Dörr, Marcus
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.

VL - 127
IS - 5
ER -