The role of DNA methylation patterns in complex phenotypes remains unclear. To explore this question, we adapted our methods for rare variant analysis to characterize genome-wide murine DNA hybridization array to investigate methylation at CpG islands, shores, and regulatory elements. We have applied this platform to compare age and tissue- specific methylation differences in the brain and spleen of young and aged mice. As expected from prior studies, there are clear global differences in organ-specific, but not age-specific, methylation due mostly to changes at repetitive elements. Surprisingly, out of 200,000 loci there were only 946 differentially methylated cytosines (DMCs) between young and old samples (529 hypermethylated, 417 hypomethylated in aged mice) compared to thousands of tissue-specific DMCs. Hypermethylated loci were clustered around the promoter region of Sfi1, exon 2 of Slc11a2, Drg1, Esr1 and Foxa2 transcription factor binding sites. In particular, there were 75 hypermethylated Foxa2 binding sites across a 2.7 Mb region of chromosome 11. Hypomethylated loci were clustered around Mid1, Isoc2b and genome-wide loci with binding sites for Foxa2 and Esr1, which are known to play important roles in development and aging. These data suggest discreet tissue-independent methylation changes associated with aging processes such as cell division (Sfi1, Mid1), energy production (Drg1, Isoc2b) and cell death (Foxa2, Esr1).

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Psoriasis is a chronic, multisystemic, inflammatory disease that exhibits a wide array of clinical presentations and is associated with high disease burden. Advancements in our understanding of the pathophysiology of psoriasis have led to the development of novel therapeutic modalities known as biologics that inhibit the action of pro-inflammatory cytokines, offering a more targeted therapeutic approach and improved safety profile compared to traditional systemic agents. Psoriasis disease severity is usually the main driver when it comes to selecting the appropriate biologic for any given patient; however, with an increasing number of biologics from which to choose, one pressing question that is increasingly more common in clinical practice is, “How do we select the ‘right’ treatment for each patient?” We performed a review of the literature on biologic use in patients with psoriasis with a focus on specific systemic comorbidities. Here, we summarize currently available recommendations based on available studies.