Identification of genetic interaction with risk factors using a time-to-event model

Mariza de Andrade, Sebastian M. Armasu, Bryan M. McCauley, Tanya M. Petterson, John A. Heit

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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).

Original languageEnglish (US)
Article number1228
JournalInternational journal of environmental research and public health
Issue number10
StatePublished - Oct 15 2017
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgments: This manuscript was funded, in part, by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute (HL66216 and HL83141) and the National Human Genome Research Institute (HG04735 and HG06379), Mayo Clinic Women’s Health Research Center award and Mayo Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.


  • Genetic variation
  • Genome-wide association study
  • Pregnancy complications
  • Risk factors
  • Venous thromboembolism


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