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1.	Wain, LV, et al. (author) Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure 2011 In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:10, s. 1005-U122 Journal article (peer-reviewed)
2.	Debette, Stephanie, et al. (author) Identification of cis- and trans-Acting Genetic Variants Explaining Up to Half the Variation in Circulating Vascular Endothelial Growth Factor Levels 2011 In: Circulation Research. - 0009-7330 .- 1524-4571. ; 109:5, s. 554-563 Journal article (peer-reviewed)abstract 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<5x10(-8)). We found evidence of replication for the most significant associations in both replication datasets. In a conditional genome-wide association study, 4 SNPs mapping to 3 chromosomal regions were independently associated with circulating VEGF levels: rs6921438 and rs4416670 (6p21.1, P=6.11x10(-506) and P=1.47x10(-12)), rs6993770 (8q23.1, P=2.50x10(-16)), and rs10738760 (9p24.2, P=1.96x10(-34)). A genetic score including these 4 SNPs explained 48% of the heritability of serum VEGF levels. Six of the SNPs that reached genome-wide significance in the genome-wide association study were significantly associated with VEGF messenger RNA levels in peripheral blood mononuclear cells. Ingenuity pathway analyses showed found plausible biological links between VEGF and 2 novel genes in these loci (ZFPM2 and VLDLR). Conclusions: Genetic variants explaining up to half the heritability of serum VEGF levels were identified. These new insights provide important clues to the pathways regulating circulating VEGF levels.

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Type of publication: journal article (2)

Type of content: peer-reviewed (2)

Author/Editor: Erdmann, J. (1); Zhang, F. (1); Hottenga, JJ (1); Willemsen, G (1); Davies, G (1); Schmidt, H. (1); show more...; Gyllensten, Ulf B. (1); Scott, J. (1); Tanaka, T. (1); Boomsma, DI (1); Amin, N (1); van Duijn, CM (1); Groop, Leif (1); Loos, RJF (1); Hadley, D. (1); Lathrop, M (1); Laan, M (1); Lind, Lars (1); Johnson, T. (1); Alizadeh, BZ (1); Melander, Olle (1); Sala, C (1); Trompet, S (1); Bis, JC (1); Lopez, LM (1); Milaneschi, Y (1); Smith, AV (1); De Geus, EJC (1); DeStefano, AL (1); Ferrucci, L (1); Gudnason, V (1); Hofman, A (1); Jukema, JW (1); Psaty, BM (1); Schmidt, R (1); Singleton, A (1); Uitterlinden, AG (1); Volzke, H (1); Deary, IJ (1); Fornage, M (1); Debette, S (1); Penninx, BW (1); Pistis, G (1); Tobin, MD (1); Wain, LV (1); Elliott, P (1); Nolte, IM (1); Volker, U (1); Hamsten, A (1); Boerwinkle, E (1); show less...

University: Uppsala University (2); Karolinska Institutet (2); Lund University (1)

Language: English (2)

Research subject (UKÄ/SCB): Medical and Health Sciences (1)

Year: 2011 (2)Undo refine

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