A functional genomic perspective on human well-being.

TitleA functional genomic perspective on human well-being.
Publication TypeJournal Article
Year of Publication2013
AuthorsFredrickson BL, Grewen KM, Coffey KA, Algoe SB, Firestine AM, Arevalo JMG, Ma J, Cole SW
JournalProc Natl Acad Sci U S A
Date Published2013 Aug 13
KeywordsAdult, Antibodies, Computational Biology, Gene Regulatory Networks, Genome, Human, Happiness, Humans, Interferon Type I, Leukocytes, Mononuclear, Middle Aged, Models, Psychological, NF-kappa B, North Carolina, Pleasure, Quality of Life, Surveys and Questionnaires, Transcription Factor AP-1, Transcription Factors, Transcriptome

To identify molecular mechanisms underlying the prospective health advantages associated with psychological well-being, we analyzed leukocyte basal gene expression profiles in 80 healthy adults who were assessed for hedonic and eudaimonic well-being, as well as potentially confounded negative psychological and behavioral factors. Hedonic and eudaimonic well-being showed similar affective correlates but highly divergent transcriptome profiles. Peripheral blood mononuclear cells from people with high levels of hedonic well-being showed up-regulated expression of a stress-related conserved transcriptional response to adversity (CTRA) involving increased expression of proinflammatory genes and decreased expression of genes involved in antibody synthesis and type I IFN response. In contrast, high levels of eudaimonic well-being were associated with CTRA down-regulation. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity in structuring the observed differences in gene expression associated with eudaimonic well-being (reduced NF-κB and AP-1 signaling and increased IRF and STAT signaling). Transcript origin analysis identified monocytes, plasmacytoid dendritic cells, and B lymphocytes as primary cellular mediators of these dynamics. The finding that hedonic and eudaimonic well-being engage distinct gene regulatory programs despite their similar effects on total well-being and depressive symptoms implies that the human genome may be more sensitive to qualitative variations in well-being than are our conscious affective experiences.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID23898182
PubMed Central IDPMC3746929
Grant ListP30 AG017265 / AG / NIA NIH HHS / United States
P30AG107265 / AG / NIA NIH HHS / United States
R01 NR012899 / NR / NINR NIH HHS / United States
R01CA116778 / CA / NCI NIH HHS / United States
R01NR012899 / NR / NINR NIH HHS / United States