Identification of cis- and trans-Acting Genetic Variants Explaining Up to Half the Variation in Circulating Vascular Endothelial Growth Factor Levels

RATIONALE:Vascular endothelial growth factor (VEGF) affects angiogenesis, atherosclerosis, and cancer. Although the heritability of circulating VEGF levels is high, little is known about its genetic underpinnings. OBJECTIVE:Our aim was to identify genetic variants associated with circulating VEGF le...

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Veröffentlicht in:	Circulation research 2011-08, Vol.109 (5), p.554-563
Hauptverfasser:	Debette, Stephanie, Visvikis-Siest, Sophie, Chen, Ming-Huen, Ndiaye, Ndeye-Coumba, Song, Ci, Destefano, Anita, Safa, Radwan, Azimi Nezhad, Mohsen, Sawyer, Douglas, Marteau, Jean-Brice, Xanthakis, Vanessa, Siest, Gerard, Sullivan, Lisa, Pfister, Michele, Smith, Holly, Choi, Seung-Hoan, Lamont, John, Lind, Lars, Yang, Qiong, Fitzgerald, Peter, Ingelsson, Erik, Vasan, Ramachandran S, Seshadri, Sudha
Format:	Artikel
Sprache:	eng
Schlagworte:	Adolescent Adult Aged Biological and medical sciences Cohort Studies Female Fundamental and applied biological sciences. Psychology gene expression Gene Regulatory Networks - genetics Genetic Variation - genetics genome-wide association study Genome-Wide Association Study - methods growth factors Humans Male Middle Aged pathway analysis Polymorphism, Single Nucleotide - genetics Prospective Studies RNA, Messenger - biosynthesis RNA, Messenger - blood RNA, Messenger - genetics Vascular Endothelial Growth Factor A - biosynthesis Vascular Endothelial Growth Factor A - blood Vascular Endothelial Growth Factor A - genetics Vertebrates: cardiovascular system Young Adult
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Zusammenfassung:	RATIONALE:Vascular endothelial growth factor (VEGF) affects angiogenesis, atherosclerosis, and cancer. Although the heritability of circulating VEGF levels is high, little is known about its genetic underpinnings. OBJECTIVE:Our aim was to identify genetic variants associated with circulating VEGF levels, using an unbiased genome-wide approach, and to explore their functional significance with gene expression and pathway analysis. METHODS AND RESULTS:We undertook a genome-wide association study of serum VEGF levels in 3527 participants of the Framingham Heart Study, with preplanned replication in 1727 participants from 2 independent samples, the STANISLAS Family Study and the Prospective Investigation of the Vasculature in Uppsala Seniors study. One hundred forty single nucleotide polymorphism (SNPs) reached genome-wide significance (P
ISSN:	0009-7330 1524-4571 1524-4571
DOI:	10.1161/CIRCRESAHA.111.243790