||common in clinvar
rs6427196 is located in the F5/NME7 region on chromosome 1q24.2 at position 167747847. This SNP is in the 3’ untranslated region of F5. F5, also known as coagulation factor V (proaccelerin, lavile factor), encodes an essential cofactor of the blood coagulation cascade and defects in this gene have been known to result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia. Recently, this SNP has been found to be associated with venous thromboembolism (VTE). VTE, which can manifest itself as either deep venous thromboembolism (DVT) or pulmonary embolism (PE), is a common cardiovascular condition with a high mortality rate [PMID 23650146]. Annually, ~2 million adults develop DVT and approximately 600,000 PE hospitalizations and 60,000 deaths occur [PMID 8925592].
In a study done by Tang et al.[PMID 23650146], a two-stage genome-wide association study (GWAS) was conducted by first analyzing the top SNP associations for total incident VTE in CHARGE (cohorts for heart and aging research in genomic epidemiology) and then the second-stage studies were performed using data from three case-control studies: the Mayo Clinic VTE Study, the MARseille Thrombosis Association VTE Study, and a French case-control study on early-onset VT. In the CHARGE GWAS, 1,618 VTE cases were included from 44,499 participants, all of which were of European origin. From that, the top 1,047 SNPs identified as having the greatest association were analyzed in 3,231 VTE cases and 3,536 controls.
The initial CHARGE GWAS revealed that the rs6427196 G minor allele had a risk ratio (RR) of 1.82 with a 95% confidence interval (CI) of 1.58 to 2.10. The p-value of this association was 1.97 x 10-16. The second-stage analysis gave a RR of 2.31 with a 95% CI of 2.04 to 2.62 and a p-value of 2.56 x 10-38. At this point, all the studies were combined to give an overall RR and p-value which indicated rs6427196 as the highest associated SNP with VTE. The overall RR was 2.07 (95% CI = 1.89 – 2.28) and a p-value of 4.47 x 10-51.