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Genome Biology

, 8:R189

First Online: 13 September 2007Received: 02 March 2007Revised: 30 July 2007Accepted: 13 September 2007


BackgroundSocial environmental influences on human health are well established in the epidemiology literature, but their functional genomic mechanisms are unclear. The present study analyzed genome-wide transcriptional activity in people who chronically experienced high versus low levels of subjective social isolation loneliness to assess alterations in the activity of transcription control pathways that might contribute to increased adverse health outcomes in social isolates.

ResultsDNA microarray analysis identified 209 genes that were differentially expressed in circulating leukocytes from 14 high- versus low-lonely individuals, including up-regulation of genes involved in immune activation, transcription control, and cell proliferation, and down-regulation of genes supporting mature B lymphocyte function and type I interferon response. Promoter-based bioinformatic analyses showed under-expression of genes bearing anti-inflammatory glucocorticoid response elements GREs; p = 0.032 and over-expression of genes bearing response elements for pro-inflammatory NF-κB-Rel transcription factors p = 0.011. This reciprocal shift in pro- and anti-inflammatory signaling was not attributable to differences in circulating cortisol levels, or to other demographic, psychological, or medical characteristics. Additional transcription control pathways showing differential activity in bioinformatic analyses included the CREB-ATF, JAK-STAT, IRF1, C-EBP, Oct, and GATA pathways.

ConclusionThese data provide the first indication that human genome-wide transcriptional activity is altered in association with a social epidemiological risk factor. Impaired transcription of glucocorticoid response genes and increased activity of pro-inflammatory transcription control pathways provide a functional genomic explanation for elevated risk of inflammatory disease in individuals who experience chronically high levels of subjective social isolation.

AbbreviationsANCOVAanalysis of covariance

CHASRSChicago Health Aging and Social Relations Study

CRPC-reactive protein

FDRfalse discovery rate

GOGene Ontology

GRglucocorticoid receptor

GREglucocorticoid response element


IRFinterferon response factor

JAK-STATJanus kinase-signal transducer and activator of transcription

NFnuclear factor

TELiSTranscription Element Listening System

TFBMtranscription factor-binding motif.

Electronic supplementary materialThe online version of this article doi:10.1186-gb-2007-8-9-r189 contains supplementary material, which is available to authorized users.

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Author: Steve W Cole - Louise C Hawkley - Jesusa M Arevalo - Caroline Y Sung - Robert M Rose - John T Cacioppo


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