Single Nucleotide Polymorphisms (SNPs) Associated with Pulmonary Embolism (PE): A Genome-Wide Association Study (GWAS)

Factor V Leiden (F5rs6025) has been suggested as a disease-susceptibility SNP for deep vein thrombosis (DVT) but not PE. Given the significantly reduced survival after PE, identifying individuals at risk for PE is important for targeting prophylaxis and improving survival.

To identify PE disease-susceptibility genes.

We performed in silicoGWAS analyses of VTE cases using genotype data imputed to ∼2.5 million SNPs from adults with objectively-diagnosed PE ± DVT (n=745), and DVT only (n=758). We tested these SNPs for an association with PE ± DVT after adjusting for age, sex, stroke and/or myocardial infarction, and USA state of residence using unconditional logistic regression.

Of all SNPs, three were most strongly associated with PE ± DVT: one at BDH1 on chromosome (chr) 3q29 (rs1309873, OR=1.56, p=4.02E-07) and two at SLC39A10 on chr 2q32.3 (rs7578216, OR=2.55, p=4.57E-07; and rs4589778, OR=2.49, p=7.52E-07). Individually adjusting for F5 rs6025 (chr 1), F2 rs1799963 (prothrombin G20210A; chr 11) and ABO rs8176719 (ABO blood type O allele; chr 9) did not materially affect these associations. None of these three SNPs associated with PE were intragenic. BDH1 encodes for 3-hydroxybutyrate dehydrogenase 1, a key mitochondrial enzyme in fatty acid catabolism, and SLC39A10encodes for solute carrier family 39, member 10, an important protein for zinc transport.

Chromosomes 3q29 (BDH1) and 2q32.2 (SLC39A10) may harbor PE disease-susceptibility gene regions (genes). These findings require independent confirmation. If confirmed, additional studies addressing the biologic mechanisms through which these genes and/or gene regions operate to increase PE risk also will be required.

No relevant conflicts of interest to declare.