Identifying Genetic Instruments for VEGF

Single nucleotide polymorphisms (SNPs) significantly (P < 5×10^-8) related to VEGF levels were selected as instrumental variables (IVs). Since only 3 SNPs were retained after a harmonizing step at r² < 0.001, all independent variants (r² < 0.01) were retained based on European ancestry reference data from the 1000 Genomes Project. In addition, the Phenoscanner (22 (link), 23 (link)) (http://www.phenoscanner.medschl.cam.ac.uk/) search was used to check or detect whether any of these selected SNPs were strongly related to other diseases or phenotypes other than VEGF, so as to prevent a possible effect of the genetic variants on the outcome through confounding factors, known as horizontal pleiotropy. We looked up each SNP and their proxies (r² > 0.80) to check any previous associations (P <5×10^-8) with 3 potential confounders selected based on previously published studies: ulcerative colitis (24 (link)–26 (link)), interleukin (IL) levels (27 (link)–29 (link)) and hemoglobin concentration (30 (link)). Three SNPs were detected and eliminated for being associated with potential confounders (rs6920532: colitis ulcerative, rs6921438: interleukin (IL) (IL-12p70, IL-10, IL-13, IL-7 and IL-5) levels, and rs34881325: hemoglobin concentration).

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Zhang Q., Wu G., Zhang X., Zhang J., Jiang M., Zhang Y., Ding L, & Wang Y. (2023). Vascular endothelial growth factor and risk of malignant brain tumor: A genetic correlation and two-sample Mendelian randomization study. Frontiers in Oncology, 13, 991825.

Publication 2023

Colitis European Genetic variants Genomes Hemoglobin Interleukin Interleukin 10 Interleukin 12p70 Interleukin 13 Interleukin 5 Interleukin 7 Phenotypes Single nucleotide polymorphisms Ulcerative Ulcerative colitis Vegf

Corresponding Organization : Beijing Shijitan Hospital

Other organizations : Beijing Sanbo Brain Hospital

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Variable analysis

independent variables

Single nucleotide polymorphisms (SNPs) significantly (P < 5×10-8) related to VEGF levels

dependent variables

VEGF levels

control variables

Ulcerative colitis
Interleukin (IL) levels
Hemoglobin concentration

notes

The independent variables are the SNPs that are significantly related to VEGF levels.
The dependent variable is the VEGF levels.
The control variables are the potential confounding factors: ulcerative colitis, interleukin (IL) levels, and hemoglobin concentration.

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