Six Novel Loci Associated with Circulating VEGF Levels Identified by a Meta-analysis of Genome-Wide Association Studies

PLoS Genetics
Seung Hoan ChoiMarina Ciullo

Abstract

Vascular endothelial growth factor (VEGF) is an angiogenic and neurotrophic factor, secreted by endothelial cells, known to impact various physiological and disease processes from cancer to cardiovascular disease and to be pharmacologically modifiable. We sought to identify novel loci associated with circulating VEGF levels through a genome-wide association meta-analysis combining data from European-ancestry individuals and using a dense variant map from 1000 genomes imputation panel. Six discovery cohorts including 13,312 samples were analyzed, followed by in-silico and de-novo replication studies including an additional 2,800 individuals. A total of 10 genome-wide significant variants were identified at 7 loci. Four were novel loci (5q14.3, 10q21.3, 16q24.2 and 18q22.3) and the leading variants at these loci were rs114694170 (MEF2C, P = 6.79 x 10(-13)), rs74506613 (JMJD1C, P = 1.17 x 10(-19)), rs4782371 (ZFPM1, P = 1.59 x 10(-9)) and rs2639990 (ZADH2, P = 1.72 x 10(-8)), respectively. We also identified two new independent variants (rs34528081, VEGFA, P = 1.52 x 10(-18); rs7043199, VLDLR-AS1, P = 5.12 x 10(-14)) at the 3 previously identified loci and strengthened the evidence for the four previously identified SNPs (rs692143...Continue Reading

References

Sep 1, 1994·The Journal of Clinical Investigation·A E KochR M Strieter
Feb 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·M A MoroS Moncada
Aug 6, 1998·The Journal of Clinical Investigation·D A ArenbergR M Strieter
Mar 4, 1999·Digestive Diseases and Sciences·A BousvarosS Fishman
Mar 10, 1999·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·I HyodoY Kotani
Mar 25, 2000·Journal of the American College of Cardiology·Y HojoK Shimada
Dec 19, 2000·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·E TaniguchiM Sata
Mar 10, 2001·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·H.-S. MoonB. H. Woo
May 3, 2002·Respirology : Official Journal of the Asian Pacific Society of Respirology·Izumi KishiroNoboru Kaneko
Nov 27, 2002·The American Journal of Cardiology·Bernard S P ChinGregory Y H Lip
May 9, 2003·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Reiki NishimuraMakoto Fukuda
Jul 8, 2003·International Journal of Cancer. Journal International Du Cancer·Peter KripplHellmut Samonigg
May 18, 2004·Experimental Neurology·Jeffrey M Rosenstein, Janette M Krum
Jun 24, 2004·Archives of Otolaryngology--head & Neck Surgery·Jürgen BriegerWolf J Mann
Jul 20, 2004·Nature Genetics·Lei CaoMatthew J During
Feb 26, 2005·Annals of Neurology·Roberto Del BoGiacomo P Comi
Jun 9, 2005·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Haojie LiDaniel J George
Dec 27, 2005·Cellular Signalling·Xin Wang, Cathy Tournier
Sep 7, 2006·Inflammatory Bowel Diseases·Marc FerranteSeverine Vermeire
Jan 18, 2007·Annals of Human Genetics·Hind BerrahmouneSophie Visvikis-Siest
May 2, 2007·International Journal of Cancer. Journal International Du Cancer·Sabapathy P BalasubramanianMalcolm W Reed
May 5, 2007·Journal of Cancer Research and Clinical Oncology·Jeong Youp ParkSi Young Song
Jun 26, 2007·Acta Neurologica Scandinavica·I MateoO Combarros
Mar 6, 2008·Neoplasia : an International Journal for Oncology Research·Lesa A BegleyJill A Macoska
May 3, 2008·Investigative Ophthalmology & Visual Science·Debasish MaitiElia J Duh

❮ Previous
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Citations

Aug 3, 2017·Journal of the American Heart Association·Shiu Lun Au YeungC Mary Schooling
Oct 14, 2017·Circulation. Cardiovascular Genetics·Tingwei GuoUNKNOWN International 22q11.2 Consortium/Brain and Behavior Consortium*
Nov 7, 2018·Scientific Reports·Federico InnocentiKouros Owzar
Mar 17, 2020·Drug Development Research·Elisabetta MaffiolettiAlessandra Minelli
Dec 11, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Julyan Keller-BaruchJ Brent Richards
Nov 9, 2016·Journal of Basic and Clinical Physiology and Pharmacology·Eynav HarpazYitzhak Weinstein
Jun 27, 2018·Molecular Psychiatry·Tanya HorwitzChunyu Liu
Nov 9, 2018·European Archives of Psychiatry and Clinical Neuroscience·LeHoa NguyenReiji Yoshimura
Apr 16, 2020·International Journal of Molecular Sciences·Amelia CasamassimiCiro Abbondanza
Oct 21, 2020·International Journal of Environmental Research and Public Health·Rafał RudzikAndrzej Pawlik
Aug 29, 2019·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·Erifili HatziagelakiChristian Herder
Nov 2, 2019·The Journal of Sexual Medicine·Mina Cintho OzahataUNKNOWN International Component of the NHLBI Recipient Epidemiology and Donor Evaluation Study (REDS-III)
Nov 9, 2021·Frontiers in Immunology·Hui LuMeichen Sun

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Methods Mentioned

BETA
genotyping
ELISA

Software Mentioned

HaploReg
Ingenuity Pathway Analysis
GWAtoolbox package
Ingenuity Pathway Analysis IPA
R
METAL
Gene Set Enrichment Analysis ( GSEA )
R package
PLINK
MAGENTA

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