Table 2.
Results from Mendelian Randomization Studies on Three Circulating Proteins
| Mendelian Randomization Analysis on Risk of PAH* |
pQTL Variant |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Protein (Encoding Gene) | Odds Ratio | 95% Confidence Interval | P Value | Genetic Variant | Effect Allele | MAF in PAH GWAS | MAF in gnomAD v2.1.1 | pQTL Location | Variant Mapping | |
| NET4 (NTN4) | 1.55 | 1.16 | 2.08 | 0.0035 | rs17288108 | A | 0.83 | 0.87 | CIS | Missense variant of NTN4 |
| TSP2 (THBS2) | 0.83 | 0.74 | 0.94 | 0.004 | rs73043857 | A | 0.90 | 0.90 | CIS | Intronic to THBS2 |
| Endoglin (ENG) | 0.78 | 0.66 | 0.92 | 0.0042 | rs651007 | T | 0.22 | 0.20 | TRANS | Upstream of ABO gene |
Definition of abbreviations: GWAS = genome-wide association study; MAF = minor allele frequency; NET4/NTN4 = netrin-4; PAH = pulmonary arterial hypertension; pQTL = protein quantitative trait loci; TSP2/THSB2 = thrombospondin-2.
*
Effect directions in Mendelian randomization analysis were harmonized to increasing circulating protein levels for the ease of comparison.