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Int. J. Environ. Res. Public Health 2017, 14(10), 1228; doi:10.3390/ijerph14101228

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

1
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
2
Division of Epidemiology, Department of Health Sciences Research; Mayo Clinic, Rochester, MN 55905, USA
3
Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA
*
Author to whom correspondence should be addressed.
Received: 18 August 2017 / Revised: 9 October 2017 / Accepted: 11 October 2017 / Published: 15 October 2017
(This article belongs to the Special Issue Gene-Environment Interactions and Disease)
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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). View Full-Text
Keywords: genome-wide association study; genetic variation; pregnancy complications; risk factors; venous thromboembolism genome-wide association study; genetic variation; pregnancy complications; risk factors; venous thromboembolism
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MDPI and ACS Style

de Andrade, M.; Armasu, S.M.; McCauley, B.M.; Petterson, T.M.; Heit, J.A. Identification of Genetic Interaction with Risk Factors Using a Time-To-Event Model. Int. J. Environ. Res. Public Health 2017, 14, 1228.

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