Genome-wide association study of hemodynamic response to mental stress Open Access

Liu, Xi (2016)

Permanent URL: https://etd.library.emory.edu/concern/etds/2v23vt83f?locale=en
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Abstract

Abstract

Genome-wide association study of hemodynamic response to mental stress

By Xi Liu

Background: Elevated hemodynamic responses might play an important role in the progress of mental stress-induced ischemia (MSI). Former genetic studies have identified a number of genetic loci associated to baseline hemodynamic measurements including heart rate, blood pressure and their product. However, no robust genetic associations have been linked to hemodynamic response to mental stress. Our study aims to understand the genetic determinants of hemodynamic response to mental stress among the Caucasians and African Americans.

Methods: A sample of patients with coronary artery diseases (CAD), including 375 Caucasian and 161 African American patients, were investigated using a genome-wide association approach. Mental stress was induced by a designed public speaking task. Adjusted for age, sex, beta blocker use, pre-stress measure and population structure, multiple linear regression models were applied to examine the association between genome-wide SNPs and hemodynamic responses to mental stress. A meta-analysis was carried out to combine the results from African American and Caucasian participants.

Results: After correction for multiple testing, rs12229466a SNP located in TMEM312D, was significantly associated with heart rate response to mental stress (meta-analysis p-value=7.90×10-9) with beta coefficients of 3.521 (p-value= 0.00015) in African Americans, and 3.692 (p-value= 2.63×10-5) in Caucasians. SNP rs12229466 was not associated with heart rate response to physical stress. For systolic blood pressure and rate-pressure product, several SNPs were identified with suggestive association with their response to mental stress.

Conclusions: rs12229466 in TMEM312D was found to be associated with heart rate response to mental stress in CAD patients in both African American and Caucasian cohorts. Larger studies and independent replication studies in other population are needed to replicate this finding. Further functional studies to follow up this genetic locus may reveal the regulation mechanism of heart rate response to mental stress.

Keywords: Genome-wide association study, Hemodynamic response, Mental stress, Mental stress-induced ischemia, heart rate

Table of Contents

Introduction. 1
Mental Stress-Induced Ischemia (MSI)1
Clinical Importance of hemodynamic response1
Genetic Association. 3
Methods. 6
Study Population. 6
Mental-Stress Procedure. 6
GWAS Data Quality Control7
Statistical Methods. 7
Results. 10
Discussion. 13
Tables and Figures. 15
References. 26

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