Skip to main content
eScholarship
Open Access Publications from the University of California

UCLA

UCLA Previously Published Works bannerUCLA

Association between Stress Response Genes and Features of Diurnal Cortisol Curves in the Multi-Ethnic Study of Atherosclerosis: A New Multi-Phenotype Approach for Gene-Based Association Tests.

  • Author(s): He, Zihuai
  • Payne, Erin K
  • Mukherjee, Bhramar
  • Lee, Seunggeun
  • Smith, Jennifer A
  • Ware, Erin B
  • Sánchez, Brisa N
  • Seeman, Teresa E
  • Kardia, Sharon LR
  • Diez Roux, Ana V
  • et al.
Abstract

The hormone cortisol is likely to be a key mediator of the stress response that influences multiple physiologic systems that are involved in common chronic disease, including the cardiovascular system, the immune system, and metabolism. In this paper, a candidate gene approach was used to investigate genetic contributions to variability in multiple correlated features of the daily cortisol profile in a sample of European Americans, African Americans, and Hispanic Americans from the Multi-Ethnic Study of Atherosclerosis (MESA). We proposed and applied a new gene-level multiple-phenotype analysis and carried out a meta-analysis to combine the ethnicity specific results. This new analysis, instead of a more routine single marker-single phenotype approach identified a significant association between one gene (ADRB2) and cortisol features (meta-analysis p-value=0.0025), which was not identified by three other commonly used existing analytic strategies: 1. Single marker association tests involving each single cortisol feature separately; 2. Single marker association tests jointly testing for multiple cortisol features; 3. Gene-level association tests separately carried out for each single cortisol feature. The analytic strategies presented consider different hypotheses regarding genotype-phenotype association and imply different costs of multiple testing. The proposed gene-level analysis integrating multiple cortisol features across multiple ethnic groups provides new insights into the gene-cortisol association.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View