Steven W. Cole

“ Human Social Genomics
Initial indications that social environments might significantly affect the functional activity of the human genome came from studies dissecting leukocyte gene expression profiles into genetic and environmental components [8] , [9] . Gibson and colleagues found that ∼5% of genes expressed in leukocytes showed appreciable genetic regulation (e.g., via expression quantitative trait loci) , whereas >50% showed significant differences in expression across pastoral, rural, and urban social environments [9] . ”

“ Our emerging ability to monitor the molecular underpinnings of human well-being in everyday life using portable real-time RNA sequencing interpreted through evaluated molecular biomarkers such as the CTRA and BIT gene sets provides a wholly new opportunity to discover what works for us personally, long before those molecular dynamics coalesce into overt disease. ”

“ After all, each of our human genomes is fundamentally a system for converting environmental information into molecular resources according to the accumulated wisdom of 4 million years of hominid evolution, and those who stand to gain most from the insights they afford are we whose lives they create. ”

“ In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA) characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural “social signal transduction” pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. ”

“ Abstract A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. ”

“ If we judge societies at least in part by the extent to which they help each of us realize our genomically endowed potential for well-being, then the molecularly quantified self could represent one of our own society's most significant achievements. ”

“ The gene regulatory “wiring diagram” that maps specific biochemical signals to specific gene expression responses represents an evolved genomic program that was presumably adaptive under ancestral conditions but may have distinct maladaptive effects in the very different social environments of contemporary human life. A prototypic example comes from studies of social isolation, which is one of the most robust epidemiologic risk factors for chronic illness and mortality [11] . ”

“ However, we should still be able to empirically optimize our personal well-being by selecting the lifestyle components that best work for us in the context of our own particular life circumstances. Determining what works at the individual level has historically been complicated by the fact that the primary objective indicators of well-being involve disease and mortality events that generally occur decades after their environmental precipitants and leave little room for a do-over. ”

“ What else might molecular indicators of well-being tell us about the best way for humans to live? Several randomized controlled experimental studies have shown that contemplative practices such as mindfulness meditation, physical practices such as yoga and Tai Chi, and cognitive-behavioral stress management programs can all reduce proinflammatory gene expression in people confronting significant life adversity [22] , [28] – [31] . ”

“ However, scientists, policy makers, and the general public have long wondered how such animal dynamics might pertain to everyday human life. Studies of human social genomics are now clarifying which specific types of human genes are subject to social regulation and mapping the social signal transduction pathways that mediate these effects. ”

“ Adverse social responses propagate the individual's experience of social threat and thus promote continued CTRA signaling, continued proinflammatory feedback to the brain, continued suppression of prosocial behavior, continued adverse social reactions, and so forth. ”

“ Arc 2 shows how the resulting reductions in individual social behavior and altered social niche selection evoke less supportive and more hostile responses from the surrounding social network and thereby create a more adverse social environment. Effects of the exogenous social recursion loop (Arc 2) are propagated via the core social signal transduction cascade into continued CTRA activation and continued endogenous biological recursion (Arc 1) . ”

“ Transcriptomic measures of human well-being are just beginning to enter behavioral science, but their use should spread rapidly because they yield information that is qualitatively distinct from that available through other well-being assessments such as conscious introspection. ”

“ In this system, a transient environmental threat activates the core social signal transduction pathway to stimulate transcription of proinflammatory cytokine genes, as part of the CTRA. Arc 1 shows an endogenous biological feedback loop in which the proinflammatory gene products signal the brain to activate a programmed set of sickness behaviors that include reduced social motivation, fatigue, anhedonia, and negative emotional states. ”

“ This genomics-based analysis implies that positive affect alone may not be sufficient and that interventions targeting the self-transcendent approach to psychological well-being may provide the greatest parallel increments to molecular well-being. ”

“ Cavigelli, SA & Krausz, T, “Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors”, Proc Natl Acad Sci U S A 106: 22393–22398, pmid:20018726 1 2 Williams, JB; Pang, D; Delgado, B; Kocherginsky, M & Tretiakova, M, “A model of gene-environment interaction reveals altered mammary gland gene expression and increased tumor growth following social isolation”, Cancer Prev Res (Phila) 2: 850–861, pmid:19789294 ↑ Volden, PA; Wonder, EL ”