Comorbidities of Psoriasis - Exploring the Links by Network Approach

Abstract

Increasing epidemiological studies in patients with psoriasis report the frequent occurrence of one or more associated disorders. Psoriasis is associated with multiple comorbidities including autoimmune disease, neurological disorders, cardiometabolic diseases and inflammatory-bowel disease. An integrated system biology approach is utilized to decipher the molecular alliance of psoriasis with its comorbidities. An unbiased integrative network medicine methodology is adopted for the investigation of diseasome, biological process and pathways of five most common psoriasis associated comorbidities. A significant overlap was observed between genes acting in similar direction in psoriasis and its comorbidities proving the mandatory occurrence of either one of its comorbidities. The biological processes involved in inflammatory response and cell signaling formed a common basis between psoriasis and its associated comorbidities. The pathway analysis revealed the presence of few common pathways such as angiogenesis and few uncommon pathways which includes CCKR signaling map and gonadotrophin-realising hormone receptor pathway overlapping in all the comorbidities. The work shed light on few common genes and pathways that were previously overlooked. These fruitful targets may serve as a starting point for diagnosis and/or treatment of psoriasis comorbidities. The current research provides an evidence for the existence of shared component hypothesis between psoriasis and its comorbidities.

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

“…[63][64][65]. Previously, for such diseases as bronchial asthma and tuberculosis, we showed the potential role of genes concurrently linked with both of them in the pathogenesis of their comorbid relationships [35].…”

Psoriasis and Atopic Dermatitis

“…There is evidence that psoriasis may be hereditary, arising via complex interplay between multiple genes [ 4 , 5 ]. Linkage analyses suggest that susceptibility to psoriasis is associated with genes that control inflammatory immune mechanisms, the cell cycle, and skin barrier function [ 5 – 7 ].…”

Cardiometabolic Comorbidities in Psoriasis and Psoriatic Arthritis

“…Thus, in contrast to psoriatic arthritis (PsA) [ 7 ] and Crohn’s disease [ 8 ], which share genetically based pathomechanisms with psoriasis, chronic inflammation would provide the basis for the cardiovascular and metabolic comorbidities of psoriasis. On the other hand, a network approach has demonstrated a certain degree of commonality between psoriasis and some comorbidities as regards genes/proteins, biological processes and pathways; type 2 diabetes mellitus led the molecular comorbidity index followed by rheumatoid arthritis, Alzheimer’s disease, myocardial infarction and obesity [ 9 ]. Rather than genetic associations, an unfavorable lifestyle (smoking, obesity, no regular physical activity, and unhealthy diet), perhaps associated with the disease-associated inflammatory burden or in patients with psoriasis and/or PsA, might contribute to cardiovascular comorbidity in these conditions.…”