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Identification of Genetic Interaction with Risk Factors Using a Time-To-Event Model

Author

Listed:
  • Mariza De Andrade

    (Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA)

  • Sebastian M. Armasu

    (Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA)

  • Bryan M. McCauley

    (Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA)

  • Tanya M. Petterson

    (Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA)

  • John A. Heit

    (Division of Epidemiology, Department of Health Sciences Research; Mayo Clinic, Rochester, MN 55905, USA
    Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA)

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).

Suggested Citation

  • Mariza De Andrade & Sebastian M. Armasu & Bryan M. McCauley & Tanya M. Petterson & John A. Heit, 2017. "Identification of Genetic Interaction with Risk Factors Using a Time-To-Event Model," IJERPH, MDPI, vol. 14(10), pages 1-12, October.
    • Handle: RePEc:gam:jijerp:v:14:y:2017:i:10:p:1228-:d:115062
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