Open AccessVascular Endothelial Growth Factor and Ischemic Heart Disease Risk: A Mendelian Randomization Study
Author(s) -
Au Yeung Shiu Lun,
Lam Hugh Simon Hung San,
Schooling C. Mary
Publication year - 2017
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.117.005619
Subject(s) - medicine , mendelian randomization , cardiology , disease , risk factor , vascular disease , randomization , randomized controlled trial , gene , genetics , genetic variants , genotype , biology
Background Vascular endothelial growth factor ( VEGF ) has angiogenic and possibly proatherosclerotic properties. Observationally it is positively associated with cardiovascular disease, although these observations could be confounded or due to reverse causation. We assessed ischemic heart disease ( IHD ) risk by genetically predicted VEGF , ie, using Mendelian randomization. Methods and Results Single nucleotide polymorphisms ( SNP s) predicting VEGF level, at genome‐wide significance, were applied to the CARDIoGRAMplusC4D 1000 Genomes‐based genome‐wide association study IHD case (n=60 801)‐control (n=123 504) study. We obtained unconfounded estimates using instrumental variable analysis by combining the Wald estimates for each SNP using inverse variance weighting and Mendelian randomization–Egger regression. Based on 9 SNP s independently predicting VEGF (rs1740073 [ C6orf223 ], rs2375981 [ KCNV 2 ], rs2639990 [ ZADH 2 ], rs4782371 [ ZFPM 1 ], rs6921438 [ LOC 100132354 ], rs7043199 [ VLDLR ‐ AS 1 ], rs10761741 [ JMJD 1C ], rs6993770 [ ZFPM 2 ], and rs114694170 [ MEF 2C ]), VEGF was unrelated to IHD (odds ratio 0.99 per log‐transformed pg/mL, 95% CI 0.96‐1.02) using inverse variance weighting. However, Mendelian randomization–Egger regression suggested an inverse relation of VEGF with IHD (odds ratio 0.95, 95% CI 0.91‐0.99), although the association was not evident after excluding the lead SNP (rs6921438) or additionally excluding the pleiotropic SNP (rs6993770). Conclusions Our study does not provide strong evidence for a positive effect of VEGF on IHD but does not rule out the possibility that some specific types of VEGF , for which genetic predictors have not yet been identified, might play a role.