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Int J Environ Res Public Health. 2017 Oct 15;14(10). pii: E1228. doi: 10.3390/ijerph14101228.

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

Author information

1
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. mandrade@mayo.edu.
2
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. armasu.sebastian@mayo.edu.
3
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. mccauley.bryan@mayo.edu.
4
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. petterst@mayo.edu.
5
Division of Epidemiology, Department of Health Sciences Research; Mayo Clinic, Rochester, MN 55905, USA. Heit.John@mayo.edu.
6
Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA. Heit.John@mayo.edu.

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).

KEYWORDS:

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

PMID:
29036934
PMCID:
PMC5664729
DOI:
10.3390/ijerph14101228
[Indexed for MEDLINE]
Free PMC Article

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