Kristen M Brown1, Ana V Diez-Roux2, Jennifer A Smith3, Belinda L Needham4, Bhramar Mukherjee5, Erin B Ware6, Yongmei Liu7, Steven W Cole8, Teresa E Seeman9, Sharon L R Kardia10. 1. Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, United States; Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Rd, Atlanta, GA, 30322, United States. Electronic address: brownkri@umich.edu. 2. Department of Epidemiology, Dornsife School of Public Health, Drexel University, Nesbitt Hall, 3215 Market Street, Philadelphia, PA, 19104, United States. Electronic address: avd37@drexel.edu. 3. Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, United States; Survey Research Center, Institute for Social Research, University of Michigan, 426 Thompson Street, Ann Arbor, MI, 48104, United States. Electronic address: smjenn@umich.edu. 4. Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, United States. Electronic address: needhamb@umich.edu. 5. Department of Biostatistics, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, United States. Electronic address: bhramar@umich.edu. 6. Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, United States. Electronic address: ebakshis@umich.edu. 7. Department of Medicine, Division of Cardiology, Duke University Medical Center, 300 N Duke St, Durham, NC 27701. Electronic address: yongmei.liu@duke.edu. 8. Department of Medicine, Division of Hematology-Oncology, University of California-Los Angeles, 11-934 Factor Building, UCLA School of Medicine Campus - 167817, Los Angeles, CA, 90095, United States. Electronic address: steve.cole@ucla.edu. 9. Department of Medicine, University of California-Los Angeles, UCLA Med-Geri, BOX 951687, 2339 PVUB, Los Angeles, CA, 90095, United States. Electronic address: tseeman@mednet.ucla.edu. 10. Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, United States. Electronic address: skardia@umich.edu.
Abstract
BACKGROUND: Exposure to adverse social factors has been associated with an altered inflammatory profile, a risk factor for several acute and chronic diseases. Differential gene expression may be a biological mediator in the relationship. In this study, associations between a range of social factors and expression of inflammation-related genes were investigated. METHODS: Social factor and gene expression data were collected from 1,264 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA). Inflammation-related genes were identified from the Gene Ontology database. The associations between social factors and gene expression were first assessed using the Global Analysis of Covariance (Global ANCOVA) gene set enrichment test. When the global test was significant, linear regression and elastic net penalized regression were employed to identify the individual gene transcripts within each gene set associated with the social factor. RESULTS: Loneliness (p = 0.003), chronic burden (p = 0.002), and major or lifetime discrimination (p = 0.045) were significantly associated with global expression of the chronic inflammatory gene set. Of the 20 transcripts that comprise this gene set, elastic net selected 12 transcripts for loneliness, 8 for chronic burden, and 3 for major or lifetime discrimination. Major or lifetime discrimination was also associated with the inflammatory response (p = 0.029), regulation of the inflammatory response (p = 0.041), and immune response (p = 0.025) gene sets in global analyses, and 53, 136, and 26 transcripts were selected via elastic net for these gene sets respectively. There were no significant associations in linear regression analyses after adjustment for multiple testing. CONCLUSIONS: This study highlights gene expression as a biological mechanism through which social factors may affect inflammation.
BACKGROUND: Exposure to adverse social factors has been associated with an altered inflammatory profile, a risk factor for several acute and chronic diseases. Differential gene expression may be a biological mediator in the relationship. In this study, associations between a range of social factors and expression of inflammation-related genes were investigated. METHODS: Social factor and gene expression data were collected from 1,264 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA). Inflammation-related genes were identified from the Gene Ontology database. The associations between social factors and gene expression were first assessed using the Global Analysis of Covariance (Global ANCOVA) gene set enrichment test. When the global test was significant, linear regression and elastic net penalized regression were employed to identify the individual gene transcripts within each gene set associated with the social factor. RESULTS: Loneliness (p = 0.003), chronic burden (p = 0.002), and major or lifetime discrimination (p = 0.045) were significantly associated with global expression of the chronic inflammatory gene set. Of the 20 transcripts that comprise this gene set, elastic net selected 12 transcripts for loneliness, 8 for chronic burden, and 3 for major or lifetime discrimination. Major or lifetime discrimination was also associated with the inflammatory response (p = 0.029), regulation of the inflammatory response (p = 0.041), and immune response (p = 0.025) gene sets in global analyses, and 53, 136, and 26 transcripts were selected via elastic net for these gene sets respectively. There were no significant associations in linear regression analyses after adjustment for multiple testing. CONCLUSIONS: This study highlights gene expression as a biological mechanism through which social factors may affect inflammation.
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