Expression of socially sensitive genes: the multi-ethnic study of atherosclerosis

Kristen M. Brown, University of Michigan, Ann Arbor
Ana V. Diez-Roux, Drexel University
Jennifer A. Smith, University of Michigan, Ann Arbor
Belinda L. Needham, University of Michigan, Ann Arbor
Bhramar Mukherjee, Rollins School of Public Health
Erin B. Ware, University of Michigan, Ann Arbor
Yongmei Liu, Wake Forest University
Steven W. Cole, University of California, Los Angeles
Teresa E. Seeman, University of California, Los Angeles
Sharon L.R. Kardia, University of Michigan, Ann Arbor

Abstract

© 2019 Brown et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Gene expression may be an important biological mediator in associations between social factors and health. However, previous studies were limited by small sample sizes and use of differing cell types with heterogeneous expression patterns. We use a large populationbased cohort with gene expression measured solely in monocytes to investigate associations between seven social factors and expression of genes previously found to be sensitive to social factors. Methods We employ three methodological approaches: 1) omnibus test for the entire gene set (Global ANCOVA), 2) assessment of each association individually (linear regression), and 3) machine learning method that performs variable selection with correlated predictors (elastic net). Results In global analyses, significant associations with the a priori defined socially sensitive gene set were detected for major or lifetime discrimination and chronic burden (p = 0.019 and p = 0.047, respectively). Marginally significant associations were detected for loneliness and adult socioeconomic status (p = 0.066, p = 0.093, respectively). No associations were significant in linear regression analyses after accounting for multiple testing. However, a small percentage of gene expressions (up to 11%) were associated with at least one social factor using elastic net. Conclusion The Global ANCOVA and elastic net findings suggest that a small percentage of genes may be "socially sensitive," (i.e. demonstrate differential expression by social factor), yet single gene approaches such as linear regression may be ill powered to capture this relationship. Future research should further investigate the biological mechanisms through which social factors act to influence gene expression and how systemic changes in gene expression affect overall health.