This study has identified a clear genomic fingerprint of social isolation, and defined candidate transcription control pathways that may shape its expression, but several limitations must be considered when interpreting these results. First, the present findings are based on a relatively small number of individuals sampled from the low and high extremes of a social-epidemiological risk dimension, and thus require replication in larger samples that are more broadly representative of the total variation in human social phenotypes. However, it is remarkable that the size and inter-individual consistency of transcriptional alterations associated with subjective social isolation is sufficiently pronounced to reach high levels of statistical significance in a relatively small sample. It is unclear whether alterations in inflammatory signaling and gene expression would occur in other cell types besides leukocytes, or whether different patterns of transcriptional alteration might be observed in other tissues. It is also unclear whether the strong quantitative relationship between subjective social isolation and leukocyte transcriptional profiles observed here stems from a causal effect of social processes on gene expression (for example, via the neuroendocrine system), or whether
