Abstract
Background: Certain diseases can occur with and without a trigger. We use Venous Thromboembolism (VTE) as our example to identify genetic interaction with pregnancy in women with VTE during pre- or postpartum. Pregnancy is one of the major risk factors for VTE as it accounts for 10% of maternal deaths. Methods: We performed a whole genome association analysis using the Cox Proportional Hazard (CoxPH) model adjusted for covariates to identify genetic variants associated with the time-to-event of VTE related to pre- or postpartum during the childbearing age of 18–45 years using a case-only design in a cohort of women with VTE. Women with a VTE event after 45 years of age were censored and contributed only follow-up time. Results: We identified two intragenic single nucleotide polymorphisms (SNPs) at genome-wide significance in the PURB gene located on chromosome 7, and two additional intragenic SNPs, one in the LINGO2 gene on chromosome 9 and one in RDXP2 on chromosome X. Conclusions: We showed that the time-to-event model is a useful approach for identifying potential hazard-modification of the genetic variants when the event of interest (VTE) occurs due to a risk factor (pre- or post-partum).
Highlights
Venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and its complication pulmonary embolism (PE), is a common and potentially fatal disease, with an incidence of about 200 per100,000 women-years among pregnant or postpartum women, and accounting for approximately 10%of all maternal deaths [1,2,3,4,5]
In our candidate gene case-control study, we showed that the joint attributable risk for variants when the event of interest (VTE) of three main genetics risk factors (Factor V Leiden mutation, Prothrombin G20210A, and ABO blood type non-O) was 0.40 [18]
The hazard ratios (HRs) for pregnancy, oral contraceptive (OC), and hormone replacement therapy (HRT) are highly significant with the outcome, with the exception of family history
Summary
Venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and its complication pulmonary embolism (PE), is a common and potentially fatal disease, with an incidence of about 200 per100,000 women-years among pregnant or postpartum women, and accounting for approximately 10%of all maternal deaths [1,2,3,4,5]. 80% of VTE events during pregnancy are DVT and 20% are PE [9] It is well-known that hyper-coagulation, vascular damage, and venous stasis all occur in pregnancy, resulting in a relative risk of 4.3 with a. Methods: We performed a whole genome association analysis using the Cox Proportional Hazard (CoxPH) model adjusted for covariates to identify genetic variants associated with the time-to-event of VTE related to pre- or postpartum during the childbearing age of 18–45 years using a case-only design in a cohort of women with VTE. Conclusions: We showed that the time-to-event model is a useful approach for identifying potential hazard-modification of the genetic variants when the event of interest (VTE) occurs due to a risk factor (pre- or post-partum)
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