Citation

de Andrade M, Armasu SM, McCauley BM, Petterson TM, Heit JA. Int. J. Environ. Res. Public Health 2017; 14(10): e14101228.

Affiliation

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA. Heit.John@mayo.edu.

Copyright

(Copyright © 2017, MDPI: Multidisciplinary Digital Publishing Institute)

DOI

10.3390/ijerph14101228

PMID

29036934

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).

Language: en

Keywords

genetic variation; genome-wide association study; pregnancy complications; risk factors; venous thromboembolism